Skip to main content
Top
Published in: Immunity & Ageing 1/2020

01-12-2020 | Influenza Virus | Review

Aging induces B cell defects and decreased antibody responses to influenza infection and vaccination

Authors: Daniela Frasca, Bonnie B. Blomberg

Published in: Immunity & Ageing | Issue 1/2020

Login to get access

Abstract

Background

Aging is characterized by a progressive decline in the capacity of the immune system to fight influenza virus infection and to respond to vaccination. Among the several factors involved, in addition to increased frailty and high-risk conditions, the age-associated decrease in cellular and humoral immune responses plays a relevant role. This is in large part due to inflammaging, the chronic low-grade inflammatory status of the elderly, associated with intrinsic inflammation of the immune cells and decreased immune function.

Results

Aging is usually associated with reduced influenza virus-specific and influenza vaccine-specific antibody responses but some elderly individuals with higher pre-exposure antibody titers, due to a previous infection or vaccination, have less probability to get infected. Examples of this exception are the elderly individuals infected during the 2009 pandemic season who made antibodies with broader epitope recognition and higher avidity than those made by younger individuals. Several studies have allowed the identification of B cell intrinsic defects accounting for sub-optimal antibody responses of elderly individuals. These defects include 1) reduced class switch recombination, responsible for the generation of a secondary response of class switched antibodies, 2) reduced de novo somatic hypermutation of the antibody variable region, 3) reduced binding and neutralization capacity, as well as binding specificity, of the secreted antibodies, 4) increased epigenetic modifications that are associated with lower antibody responses, 5) increased frequencies of inflammatory B cell subsets, and 6) shorter telomeres.

Conclusions

Although influenza vaccination represents the most effective way to prevent influenza infection, vaccines with greater immunogenicity are needed to improve the response of elderly individuals. Recent advances in technology have made possible a broad approach to better understand the age-associated changes in immune cells, needed to design tailored vaccines and effective therapeutic strategies that will be able to improve the immune response of vulnerable individuals.
Literature
1.
go back to reference Ferrucci L, Guralnik JM, Pahor M, Corti MC, Havlik RJ. Hospital diagnoses, Medicare charges, and nursing home admissions in the year when older persons become severely disabled. JAMA. 1997;277(9):728–34.PubMedCrossRef Ferrucci L, Guralnik JM, Pahor M, Corti MC, Havlik RJ. Hospital diagnoses, Medicare charges, and nursing home admissions in the year when older persons become severely disabled. JAMA. 1997;277(9):728–34.PubMedCrossRef
3.
go back to reference Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.PubMedCrossRef Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.PubMedCrossRef
4.
go back to reference Bryl E, Vallejo AN, Weyand CM, Goronzy JJ. Down-regulation of CD28 expression by TNF-alpha. J Immunol. 2001;167(6):3231–8.PubMedCrossRef Bryl E, Vallejo AN, Weyand CM, Goronzy JJ. Down-regulation of CD28 expression by TNF-alpha. J Immunol. 2001;167(6):3231–8.PubMedCrossRef
5.
go back to reference Frasca D, Diaz A, Romero M, Landin AM, Blomberg BB. High TNF-alpha levels in resting B cells negatively correlate with their response. Exp Gerontol. 2014;54:116–22.PubMedCrossRef Frasca D, Diaz A, Romero M, Landin AM, Blomberg BB. High TNF-alpha levels in resting B cells negatively correlate with their response. Exp Gerontol. 2014;54:116–22.PubMedCrossRef
6.
go back to reference Parish ST, Wu JE, Effros RB. Modulation of T lymphocyte replicative senescence via TNF-{alpha} inhibition: role of caspase-3. J Immunol. 2009;182(7):4237–43.PubMedCrossRef Parish ST, Wu JE, Effros RB. Modulation of T lymphocyte replicative senescence via TNF-{alpha} inhibition: role of caspase-3. J Immunol. 2009;182(7):4237–43.PubMedCrossRef
7.
go back to reference Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017;542(7640):177–85.PubMedCrossRef Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017;542(7640):177–85.PubMedCrossRef
8.
go back to reference Frasca D, Blomberg BB. Inflammaging decreases adaptive and innate immune responses in mice and humans. Biogerontology. 2016;17(1):7–19.PubMedCrossRef Frasca D, Blomberg BB. Inflammaging decreases adaptive and innate immune responses in mice and humans. Biogerontology. 2016;17(1):7–19.PubMedCrossRef
9.
go back to reference Franceschi C, Garagnani P, Vitale G, Capri M, Salvioli S. Inflammaging and 'Garb-aging'. Trends Endocrinol Metab. 2017;28(3):199–212.PubMedCrossRef Franceschi C, Garagnani P, Vitale G, Capri M, Salvioli S. Inflammaging and 'Garb-aging'. Trends Endocrinol Metab. 2017;28(3):199–212.PubMedCrossRef
10.
go back to reference McElhaney JE, Verschoor CP, Andrew MK, Haynes L, Kuchel GA, Pawelec G. The immune response to influenza in older humans: beyond immune senescence. Immun Ageing. 2020;17:10.PubMedPubMedCentralCrossRef McElhaney JE, Verschoor CP, Andrew MK, Haynes L, Kuchel GA, Pawelec G. The immune response to influenza in older humans: beyond immune senescence. Immun Ageing. 2020;17:10.PubMedPubMedCentralCrossRef
11.
go back to reference Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R, Tempia S, Cohen C, Gran JM, Schanzer D, Cowling BJ, et al. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet. 2018;391(10127):1285–300.PubMedCrossRef Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R, Tempia S, Cohen C, Gran JM, Schanzer D, Cowling BJ, et al. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet. 2018;391(10127):1285–300.PubMedCrossRef
12.
13.
go back to reference Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289(2):179–86.PubMedCrossRef Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289(2):179–86.PubMedCrossRef
14.
go back to reference Louie JK, Acosta M, Winter K, Jean C, Gavali S, Schechter R, Vugia D, Harriman K, Matyas B, Glaser CA, et al. Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California. JAMA. 2009;302(17):1896–902.PubMedCrossRef Louie JK, Acosta M, Winter K, Jean C, Gavali S, Schechter R, Vugia D, Harriman K, Matyas B, Glaser CA, et al. Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California. JAMA. 2009;302(17):1896–902.PubMedCrossRef
15.
go back to reference Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62.PubMedCrossRef Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62.PubMedCrossRef
16.
go back to reference Haq K, McElhaney JE. Ageing and respiratory infections: the airway of ageing. Immunol Lett. 2014;162(1 Pt B):323–8.PubMedCrossRef Haq K, McElhaney JE. Ageing and respiratory infections: the airway of ageing. Immunol Lett. 2014;162(1 Pt B):323–8.PubMedCrossRef
17.
go back to reference Herold S, Becker C, Ridge KM, Budinger GR. Influenza virus-induced lung injury: pathogenesis and implications for treatment. Eur Respir J. 2015;45(5):1463–78.PubMedCrossRef Herold S, Becker C, Ridge KM, Budinger GR. Influenza virus-induced lung injury: pathogenesis and implications for treatment. Eur Respir J. 2015;45(5):1463–78.PubMedCrossRef
18.
go back to reference Didierlaurent A, Goulding J, Patel S, Snelgrove R, Low L, Bebien M, Lawrence T, van Rijt LS, Lambrecht BN, Sirard JC, et al. Sustained desensitization to bacterial toll-like receptor ligands after resolution of respiratory influenza infection. J Exp Med. 2008;205(2):323–9.PubMedPubMedCentralCrossRef Didierlaurent A, Goulding J, Patel S, Snelgrove R, Low L, Bebien M, Lawrence T, van Rijt LS, Lambrecht BN, Sirard JC, et al. Sustained desensitization to bacterial toll-like receptor ligands after resolution of respiratory influenza infection. J Exp Med. 2008;205(2):323–9.PubMedPubMedCentralCrossRef
19.
go back to reference Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–13.PubMedPubMedCentralCrossRef Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–13.PubMedPubMedCentralCrossRef
20.
go back to reference Ding Q, Lu P, Fan Y, Xia Y, Liu M. The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China. J Med Virol. 2020. Ding Q, Lu P, Fan Y, Xia Y, Liu M. The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China. J Med Virol. 2020.
21.
go back to reference Kim D, Quinn J, Pinsky B, Shah NH, Brown I. Rates of co-infection between SARS-CoV-2 and other respiratory pathogens. JAMA. 2020. Kim D, Quinn J, Pinsky B, Shah NH, Brown I. Rates of co-infection between SARS-CoV-2 and other respiratory pathogens. JAMA. 2020.
23.
go back to reference Thindwa D, Garcia Quesada M, Liu Y, Bennett J, Cohen C, Knoll MD, von Gottberg A, Hayford K, Flasche S. Use of seasonal influenza and pneumococcal polysaccharide vaccines in older adults to reduce COVID-19 mortality. Vaccine. 2020;38(34):5398–401.PubMedPubMedCentralCrossRef Thindwa D, Garcia Quesada M, Liu Y, Bennett J, Cohen C, Knoll MD, von Gottberg A, Hayford K, Flasche S. Use of seasonal influenza and pneumococcal polysaccharide vaccines in older adults to reduce COVID-19 mortality. Vaccine. 2020;38(34):5398–401.PubMedPubMedCentralCrossRef
24.
go back to reference Wei CJ, Boyington JC, Dai K, Houser KV, Pearce MB, Kong WP, Yang ZY, Tumpey TM, Nabel GJ. Cross-neutralization of 1918 and 2009 influenza viruses: role of glycans in viral evolution and vaccine design. Sci Transl Med. 2010;2(24):24ra21.PubMedPubMedCentralCrossRef Wei CJ, Boyington JC, Dai K, Houser KV, Pearce MB, Kong WP, Yang ZY, Tumpey TM, Nabel GJ. Cross-neutralization of 1918 and 2009 influenza viruses: role of glycans in viral evolution and vaccine design. Sci Transl Med. 2010;2(24):24ra21.PubMedPubMedCentralCrossRef
25.
go back to reference Verma N, Dimitrova M, Carter DM, Crevar CJ, Ross TM, Golding H, Khurana S. Influenza virus H1N1pdm09 infections in the young and old: evidence of greater antibody diversity and affinity for the hemagglutinin globular head domain (HA1 domain) in the elderly than in young adults and children. J Virol. 2012;86(10):5515–22.PubMedPubMedCentralCrossRef Verma N, Dimitrova M, Carter DM, Crevar CJ, Ross TM, Golding H, Khurana S. Influenza virus H1N1pdm09 infections in the young and old: evidence of greater antibody diversity and affinity for the hemagglutinin globular head domain (HA1 domain) in the elderly than in young adults and children. J Virol. 2012;86(10):5515–22.PubMedPubMedCentralCrossRef
27.
go back to reference Murasko DM, Bernstein ED, Gardner EM, Gross P, Munk G, Dran S, Abrutyn E. Role of humoral and cell-mediated immunity in protection from influenza disease after immunization of healthy elderly. Exp Gerontol. 2002;37(2–3):427–39.PubMedCrossRef Murasko DM, Bernstein ED, Gardner EM, Gross P, Munk G, Dran S, Abrutyn E. Role of humoral and cell-mediated immunity in protection from influenza disease after immunization of healthy elderly. Exp Gerontol. 2002;37(2–3):427–39.PubMedCrossRef
28.
go back to reference Burlington DB, Clements ML, Meiklejohn G, Phelan M, Murphy BR. Hemagglutinin-specific antibody responses in immunoglobulin G, a, and M isotypes as measured by enzyme-linked immunosorbent assay after primary or secondary infection of humans with influenza A virus. Infect Immun. 1983;41(2):540–5.PubMedPubMedCentralCrossRef Burlington DB, Clements ML, Meiklejohn G, Phelan M, Murphy BR. Hemagglutinin-specific antibody responses in immunoglobulin G, a, and M isotypes as measured by enzyme-linked immunosorbent assay after primary or secondary infection of humans with influenza A virus. Infect Immun. 1983;41(2):540–5.PubMedPubMedCentralCrossRef
29.
go back to reference McMurry JA, Johansson BE, De Groot AS. A call to cellular & humoral arms: enlisting cognate T cell help to develop broad-spectrum vaccines against influenza A. Hum Vaccin. 2008;4(2):148–57.PubMedCrossRef McMurry JA, Johansson BE, De Groot AS. A call to cellular & humoral arms: enlisting cognate T cell help to develop broad-spectrum vaccines against influenza A. Hum Vaccin. 2008;4(2):148–57.PubMedCrossRef
30.
go back to reference Wrammert J, Smith K, Miller J, Langley WA, Kokko K, Larsen C, Zheng NY, Mays I, Garman L, Helms C, et al. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature. 2008;453(7195):667–71.PubMedPubMedCentralCrossRef Wrammert J, Smith K, Miller J, Langley WA, Kokko K, Larsen C, Zheng NY, Mays I, Garman L, Helms C, et al. Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature. 2008;453(7195):667–71.PubMedPubMedCentralCrossRef
31.
go back to reference Corti D, Suguitan AL Jr, Pinna D, Silacci C, Fernandez-Rodriguez BM, Vanzetta F, Santos C, Luke CJ, Torres-Velez FJ, Temperton NJ, et al. Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine. J Clin Invest. 2010;120(5):1663–73.PubMedPubMedCentralCrossRef Corti D, Suguitan AL Jr, Pinna D, Silacci C, Fernandez-Rodriguez BM, Vanzetta F, Santos C, Luke CJ, Torres-Velez FJ, Temperton NJ, et al. Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine. J Clin Invest. 2010;120(5):1663–73.PubMedPubMedCentralCrossRef
32.
go back to reference Saurwein-Teissl M, Lung TL, Marx F, Gschosser C, Asch E, Blasko I, Parson W, Bock G, Schonitzer D, Trannoy E, et al. Lack of antibody production following immunization in old age: association with CD8(+)CD28(−) T cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines. J Immunol. 2002;168(11):5893–9.PubMedCrossRef Saurwein-Teissl M, Lung TL, Marx F, Gschosser C, Asch E, Blasko I, Parson W, Bock G, Schonitzer D, Trannoy E, et al. Lack of antibody production following immunization in old age: association with CD8(+)CD28(−) T cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines. J Immunol. 2002;168(11):5893–9.PubMedCrossRef
33.
go back to reference Andrews SF, Kaur K, Pauli NT, Huang M, Huang Y, Wilson PC. High preexisting serological antibody levels correlate with diversification of the influenza vaccine response. J Virol. 2015;89(6):3308–17.PubMedPubMedCentralCrossRef Andrews SF, Kaur K, Pauli NT, Huang M, Huang Y, Wilson PC. High preexisting serological antibody levels correlate with diversification of the influenza vaccine response. J Virol. 2015;89(6):3308–17.PubMedPubMedCentralCrossRef
34.
go back to reference Mosterin Hopping A, McElhaney J, Fonville JM, Powers DC, Beyer WEP, Smith DJ. The confounded effects of age and exposure history in response to influenza vaccination. Vaccine. 2016;34(4):540–6.PubMedCrossRef Mosterin Hopping A, McElhaney J, Fonville JM, Powers DC, Beyer WEP, Smith DJ. The confounded effects of age and exposure history in response to influenza vaccination. Vaccine. 2016;34(4):540–6.PubMedCrossRef
35.
go back to reference Young B, Zhao X, Cook AR, Parry CM, Wilder-Smith A, MCIC. Do antibody responses to the influenza vaccine persist year-round in the elderly? A systematic review and meta-analysis. Vaccine. 2017;35(2):212–21.PubMedCrossRef Young B, Zhao X, Cook AR, Parry CM, Wilder-Smith A, MCIC. Do antibody responses to the influenza vaccine persist year-round in the elderly? A systematic review and meta-analysis. Vaccine. 2017;35(2):212–21.PubMedCrossRef
36.
go back to reference Gross PA, Hermogenes AW, Sacks HS, Lau J, Levandowski RA. The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Ann Intern Med. 1995;123(7):518–27.PubMedCrossRef Gross PA, Hermogenes AW, Sacks HS, Lau J, Levandowski RA. The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Ann Intern Med. 1995;123(7):518–27.PubMedCrossRef
37.
go back to reference Simonsen L, Taylor RJ, Viboud C, Miller MA, Jackson LA. Mortality benefits of influenza vaccination in elderly people: an ongoing controversy. Lancet Infect Dis. 2007;7(10):658–66.PubMedCrossRef Simonsen L, Taylor RJ, Viboud C, Miller MA, Jackson LA. Mortality benefits of influenza vaccination in elderly people: an ongoing controversy. Lancet Infect Dis. 2007;7(10):658–66.PubMedCrossRef
38.
go back to reference Vu T, Farish S, Jenkins M, Kelly H. A meta-analysis of effectiveness of influenza vaccine in persons aged 65 years and over living in the community. Vaccine. 2002;20(13–14):1831–6.PubMedCrossRef Vu T, Farish S, Jenkins M, Kelly H. A meta-analysis of effectiveness of influenza vaccine in persons aged 65 years and over living in the community. Vaccine. 2002;20(13–14):1831–6.PubMedCrossRef
39.
go back to reference Castrucci MR. Factors affecting immune responses to the influenza vaccine. Hum Vaccin Immunother. 2018;14(3):637–46.PubMedCrossRef Castrucci MR. Factors affecting immune responses to the influenza vaccine. Hum Vaccin Immunother. 2018;14(3):637–46.PubMedCrossRef
41.
go back to reference Nakaya HI, Hagan T, Duraisingham SS, Lee EK, Kwissa M, Rouphael N, Frasca D, Gersten M, Mehta AK, Gaujoux R, et al. Systems analysis of immunity to influenza vaccination across multiple years and in diverse populations reveals shared molecular signatures. Immunity. 2015;43(6):1186–98.PubMedPubMedCentralCrossRef Nakaya HI, Hagan T, Duraisingham SS, Lee EK, Kwissa M, Rouphael N, Frasca D, Gersten M, Mehta AK, Gaujoux R, et al. Systems analysis of immunity to influenza vaccination across multiple years and in diverse populations reveals shared molecular signatures. Immunity. 2015;43(6):1186–98.PubMedPubMedCentralCrossRef
42.
go back to reference Team H-CSP, Consortium H-I. Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses. Sci Immunol. 2017;2(14):eaal4656. Team H-CSP, Consortium H-I. Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses. Sci Immunol. 2017;2(14):eaal4656.
43.
go back to reference Tsang JS, Schwartzberg PL, Kotliarov Y, Biancotto A, Xie Z, Germain RN, Wang E, Olnes MJ, Narayanan M, Golding H, et al. Global analyses of human immune variation reveal baseline predictors of postvaccination responses. Cell. 2014;157(2):499–513.PubMedPubMedCentralCrossRef Tsang JS, Schwartzberg PL, Kotliarov Y, Biancotto A, Xie Z, Germain RN, Wang E, Olnes MJ, Narayanan M, Golding H, et al. Global analyses of human immune variation reveal baseline predictors of postvaccination responses. Cell. 2014;157(2):499–513.PubMedPubMedCentralCrossRef
44.
go back to reference Furman D, Jojic V, Kidd B, Shen-Orr S, Price J, Jarrell J, Tse T, Huang H, Lund P, Maecker HT, et al. Apoptosis and other immune biomarkers predict influenza vaccine responsiveness. Mol Syst Biol. 2013;9:659.PubMedPubMedCentralCrossRef Furman D, Jojic V, Kidd B, Shen-Orr S, Price J, Jarrell J, Tse T, Huang H, Lund P, Maecker HT, et al. Apoptosis and other immune biomarkers predict influenza vaccine responsiveness. Mol Syst Biol. 2013;9:659.PubMedPubMedCentralCrossRef
45.
go back to reference Furman D, Hejblum BP, Simon N, Jojic V, Dekker CL, Thiebaut R, Tibshirani RJ, Davis MM. Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc Natl Acad Sci U S A. 2014;111(2):869–74.PubMedCrossRef Furman D, Hejblum BP, Simon N, Jojic V, Dekker CL, Thiebaut R, Tibshirani RJ, Davis MM. Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc Natl Acad Sci U S A. 2014;111(2):869–74.PubMedCrossRef
46.
go back to reference Kennedy RB, Ovsyannikova IG, Haralambieva IH, Oberg AL, Zimmermann MT, Grill DE, Poland GA. Immunosenescence-related Transcriptomic and immunologic changes in older individuals following influenza vaccination. Front Immunol. 2016;7:450.PubMedPubMedCentralCrossRef Kennedy RB, Ovsyannikova IG, Haralambieva IH, Oberg AL, Zimmermann MT, Grill DE, Poland GA. Immunosenescence-related Transcriptomic and immunologic changes in older individuals following influenza vaccination. Front Immunol. 2016;7:450.PubMedPubMedCentralCrossRef
47.
go back to reference Voigt EA, Ovsyannikova IG, Kennedy RB, Grill DE, Goergen KM, Schaid DJ, Poland GA. Sex differences in older Adults' immune responses to seasonal influenza vaccination. Front Immunol. 2019;10:180.PubMedPubMedCentralCrossRef Voigt EA, Ovsyannikova IG, Kennedy RB, Grill DE, Goergen KM, Schaid DJ, Poland GA. Sex differences in older Adults' immune responses to seasonal influenza vaccination. Front Immunol. 2019;10:180.PubMedPubMedCentralCrossRef
48.
go back to reference Avey S, Mohanty S, Chawla DG, Meng H, Bandaranayake T, Ueda I, Zapata HJ, Park K, Blevins TP, Tsang S, et al. Seasonal variability and shared molecular signatures of inactivated influenza vaccination in Young and older adults. J Immunol. 2020;204(6):1661–73.PubMedCrossRef Avey S, Mohanty S, Chawla DG, Meng H, Bandaranayake T, Ueda I, Zapata HJ, Park K, Blevins TP, Tsang S, et al. Seasonal variability and shared molecular signatures of inactivated influenza vaccination in Young and older adults. J Immunol. 2020;204(6):1661–73.PubMedCrossRef
49.
go back to reference Rogers LRK, de Los CG, Mias GI. Microarray gene expression dataset re-analysis reveals variability in influenza infection and vaccination. Front Immunol. 2019;10:2616.PubMedPubMedCentralCrossRef Rogers LRK, de Los CG, Mias GI. Microarray gene expression dataset re-analysis reveals variability in influenza infection and vaccination. Front Immunol. 2019;10:2616.PubMedPubMedCentralCrossRef
50.
go back to reference Thakar J, Mohanty S, West AP, Joshi SR, Ueda I, Wilson J, Meng H, Blevins TP, Tsang S, Trentalange M, et al. Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination. Aging (Albany NY). 2015;7(1):38–52.CrossRef Thakar J, Mohanty S, West AP, Joshi SR, Ueda I, Wilson J, Meng H, Blevins TP, Tsang S, Trentalange M, et al. Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination. Aging (Albany NY). 2015;7(1):38–52.CrossRef
51.
go back to reference Derhovanessian E, Theeten H, Hahnel K, Van Damme P, Cools N, Pawelec G. Cytomegalovirus-associated accumulation of late-differentiated CD4 T-cells correlates with poor humoral response to influenza vaccination. Vaccine. 2013;31(4):685–90.PubMedCrossRef Derhovanessian E, Theeten H, Hahnel K, Van Damme P, Cools N, Pawelec G. Cytomegalovirus-associated accumulation of late-differentiated CD4 T-cells correlates with poor humoral response to influenza vaccination. Vaccine. 2013;31(4):685–90.PubMedCrossRef
52.
go back to reference McElhaney JE, Ewen C, Zhou X, Kane KP, Xie D, Hager WD, Barry MB, Kleppinger A, Wang Y, Bleackley RC. Granzyme B: correlates with protection and enhanced CTL response to influenza vaccination in older adults. Vaccine. 2009;27(18):2418–25.PubMedPubMedCentralCrossRef McElhaney JE, Ewen C, Zhou X, Kane KP, Xie D, Hager WD, Barry MB, Kleppinger A, Wang Y, Bleackley RC. Granzyme B: correlates with protection and enhanced CTL response to influenza vaccination in older adults. Vaccine. 2009;27(18):2418–25.PubMedPubMedCentralCrossRef
53.
go back to reference McElhaney JE, Zhou X, Talbot HK, Soethout E, Bleackley RC, Granville DJ, Pawelec G. The unmet need in the elderly: how immunosenescence, CMV infection, co-morbidities and frailty are a challenge for the development of more effective influenza vaccines. Vaccine. 2012;30(12):2060–7.PubMedPubMedCentralCrossRef McElhaney JE, Zhou X, Talbot HK, Soethout E, Bleackley RC, Granville DJ, Pawelec G. The unmet need in the elderly: how immunosenescence, CMV infection, co-morbidities and frailty are a challenge for the development of more effective influenza vaccines. Vaccine. 2012;30(12):2060–7.PubMedPubMedCentralCrossRef
54.
go back to reference Beli E, Clinthorne JF, Duriancik DM, Hwang I, Kim S, Gardner EM. Natural killer cell function is altered during the primary response of aged mice to influenza infection. Mech Ageing Dev. 2011;132(10):503–10.PubMedPubMedCentralCrossRef Beli E, Clinthorne JF, Duriancik DM, Hwang I, Kim S, Gardner EM. Natural killer cell function is altered during the primary response of aged mice to influenza infection. Mech Ageing Dev. 2011;132(10):503–10.PubMedPubMedCentralCrossRef
55.
go back to reference Przemska-Kosicka A, Childs CE, Maidens C, Dong H, Todd S, Gosney MA, Tuohy KM, Yaqoob P. Age-related changes in the natural killer cell response to seasonal influenza vaccination are not influenced by a Synbiotic: a randomised controlled trial. Front Immunol. 2018;9:591.PubMedPubMedCentralCrossRef Przemska-Kosicka A, Childs CE, Maidens C, Dong H, Todd S, Gosney MA, Tuohy KM, Yaqoob P. Age-related changes in the natural killer cell response to seasonal influenza vaccination are not influenced by a Synbiotic: a randomised controlled trial. Front Immunol. 2018;9:591.PubMedPubMedCentralCrossRef
56.
go back to reference Mohanty S, Joshi SR, Ueda I, Wilson J, Blevins TP, Siconolfi B, Meng H, Devine L, Raddassi K, Tsang S, et al. Prolonged proinflammatory cytokine production in monocytes modulated by interleukin 10 after influenza vaccination in older adults. J Infect Dis. 2015;211(7):1174–84.PubMedCrossRef Mohanty S, Joshi SR, Ueda I, Wilson J, Blevins TP, Siconolfi B, Meng H, Devine L, Raddassi K, Tsang S, et al. Prolonged proinflammatory cytokine production in monocytes modulated by interleukin 10 after influenza vaccination in older adults. J Infect Dis. 2015;211(7):1174–84.PubMedCrossRef
57.
go back to reference Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L, Chen S, Towle V, Belshe RB, Fikrig E, et al. Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol. 2010;184(5):2518–27.PubMedCrossRef Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L, Chen S, Towle V, Belshe RB, Fikrig E, et al. Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol. 2010;184(5):2518–27.PubMedCrossRef
58.
go back to reference Frasca D, Diaz A, Romero M, Ferracci F, Blomberg BB. MicroRNAs miR-155 and miR-16 decrease AID and E47 in B cells from elderly individuals. J Immunol. 2015;195(5):2134–40.PubMedCrossRef Frasca D, Diaz A, Romero M, Ferracci F, Blomberg BB. MicroRNAs miR-155 and miR-16 decrease AID and E47 in B cells from elderly individuals. J Immunol. 2015;195(5):2134–40.PubMedCrossRef
59.
go back to reference Frasca D, Diaz A, Romero M, Landin AM, Phillips M, Lechner SC, Ryan JG, Blomberg BB. Intrinsic defects in B cell response to seasonal influenza vaccination in elderly humans. Vaccine. 2010;28(51):8077–84.PubMedPubMedCentralCrossRef Frasca D, Diaz A, Romero M, Landin AM, Phillips M, Lechner SC, Ryan JG, Blomberg BB. Intrinsic defects in B cell response to seasonal influenza vaccination in elderly humans. Vaccine. 2010;28(51):8077–84.PubMedPubMedCentralCrossRef
60.
go back to reference Frasca D, Diaz A, Romero M, Mendez NV, Landin AM, Blomberg BB. Effects of age on H1N1-specific serum IgG1 and IgG3 levels evaluated during the 2011-2012 influenza vaccine season. Immun Ageing. 2013;10(1):14.PubMedPubMedCentralCrossRef Frasca D, Diaz A, Romero M, Mendez NV, Landin AM, Blomberg BB. Effects of age on H1N1-specific serum IgG1 and IgG3 levels evaluated during the 2011-2012 influenza vaccine season. Immun Ageing. 2013;10(1):14.PubMedPubMedCentralCrossRef
61.
go back to reference Frasca D, Diaz A, Romero M, Mendez NV, Landin AM, Ryan JG, Blomberg BB. Young and elderly patients with type 2 diabetes have optimal B cell responses to the seasonal influenza vaccine. Vaccine. 2013;31(35):3603–10.PubMedPubMedCentralCrossRef Frasca D, Diaz A, Romero M, Mendez NV, Landin AM, Ryan JG, Blomberg BB. Young and elderly patients with type 2 diabetes have optimal B cell responses to the seasonal influenza vaccine. Vaccine. 2013;31(35):3603–10.PubMedPubMedCentralCrossRef
62.
go back to reference Frasca D, Diaz A, Romero M, Phillips M, Mendez NV, Landin AM, Blomberg BB. Unique biomarkers for B-cell function predict the serum response to pandemic H1N1 influenza vaccine. Int Immunol. 2012. Frasca D, Diaz A, Romero M, Phillips M, Mendez NV, Landin AM, Blomberg BB. Unique biomarkers for B-cell function predict the serum response to pandemic H1N1 influenza vaccine. Int Immunol. 2012.
63.
go back to reference Frasca D, Ferracci F, Diaz A, Romero M, Lechner S, Blomberg BB. Obesity decreases B cell responses in young and elderly individuals. Obesity (Silver Spring). 2016;24(3):615–25.CrossRef Frasca D, Ferracci F, Diaz A, Romero M, Lechner S, Blomberg BB. Obesity decreases B cell responses in young and elderly individuals. Obesity (Silver Spring). 2016;24(3):615–25.CrossRef
64.
go back to reference Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell. 2000;102(5):553–63.PubMedCrossRef Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell. 2000;102(5):553–63.PubMedCrossRef
65.
go back to reference Frasca D, Landin AM, Lechner SC, Ryan JG, Schwartz R, Riley RL, Blomberg BB. Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells. J Immunol. 2008;180(8):5283–90.PubMedCrossRef Frasca D, Landin AM, Lechner SC, Ryan JG, Schwartz R, Riley RL, Blomberg BB. Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells. J Immunol. 2008;180(8):5283–90.PubMedCrossRef
66.
go back to reference Sayegh CE, Quong MW, Agata Y, Murre C. E-proteins directly regulate expression of activation-induced deaminase in mature B cells. Nat Immunol. 2003;4(6):586–93.PubMedCrossRef Sayegh CE, Quong MW, Agata Y, Murre C. E-proteins directly regulate expression of activation-induced deaminase in mature B cells. Nat Immunol. 2003;4(6):586–93.PubMedCrossRef
67.
go back to reference Gonda H, Sugai M, Nambu Y, Katakai T, Agata Y, Mori KJ, Yokota Y, Shimizu A. The balance between Pax5 and Id2 activities is the key to AID gene expression. J Exp Med. 2003;198(9):1427–37.PubMedPubMedCentralCrossRef Gonda H, Sugai M, Nambu Y, Katakai T, Agata Y, Mori KJ, Yokota Y, Shimizu A. The balance between Pax5 and Id2 activities is the key to AID gene expression. J Exp Med. 2003;198(9):1427–37.PubMedPubMedCentralCrossRef
68.
go back to reference Hauser J, Grundstrom C, Kumar R, Grundstrom T. Regulated localization of an AID complex with E2A, PAX5 and IRF4 at the Igh locus. Mol Immunol. 2016;80:78–90.PubMedCrossRef Hauser J, Grundstrom C, Kumar R, Grundstrom T. Regulated localization of an AID complex with E2A, PAX5 and IRF4 at the Igh locus. Mol Immunol. 2016;80:78–90.PubMedCrossRef
69.
go back to reference Nipper AJ, Smithey MJ, Shah RC, Canaday DH, Landay AL. Diminished antibody response to influenza vaccination is characterized by expansion of an age-associated B-cell population with low PAX5. Clin Immunol. 2018;193:80–7.PubMedCrossRef Nipper AJ, Smithey MJ, Shah RC, Canaday DH, Landay AL. Diminished antibody response to influenza vaccination is characterized by expansion of an age-associated B-cell population with low PAX5. Clin Immunol. 2018;193:80–7.PubMedCrossRef
70.
go back to reference Frasca D, Diaz A, Romero M, Thaller S, Blomberg BB. Metabolic requirements of human pro-inflammatory B cells in aging and obesity. PLoS One. 2019;14(7):e0219545.PubMedPubMedCentralCrossRef Frasca D, Diaz A, Romero M, Thaller S, Blomberg BB. Metabolic requirements of human pro-inflammatory B cells in aging and obesity. PLoS One. 2019;14(7):e0219545.PubMedPubMedCentralCrossRef
71.
go back to reference Frasca D, Diaz A, Romero M, Blomberg BB. The generation of memory B cells is maintained, but the antibody response is not, in the elderly after repeated influenza immunizations. Vaccine. 2016;34(25):2834–40.PubMedPubMedCentralCrossRef Frasca D, Diaz A, Romero M, Blomberg BB. The generation of memory B cells is maintained, but the antibody response is not, in the elderly after repeated influenza immunizations. Vaccine. 2016;34(25):2834–40.PubMedPubMedCentralCrossRef
72.
go back to reference Khurana S, Frasca D, Blomberg B, Golding H. AID activity in B cells strongly correlates with polyclonal antibody affinity maturation in-vivo following pandemic 2009-H1N1 vaccination in humans. PLoS Pathog. 2012;8(9):e1002920.PubMedPubMedCentralCrossRef Khurana S, Frasca D, Blomberg B, Golding H. AID activity in B cells strongly correlates with polyclonal antibody affinity maturation in-vivo following pandemic 2009-H1N1 vaccination in humans. PLoS Pathog. 2012;8(9):e1002920.PubMedPubMedCentralCrossRef
73.
go back to reference Sasaki S, Sullivan M, Narvaez CF, Holmes TH, Furman D, Zheng NY, Nishtala M, Wrammert J, Smith K, James JA, et al. Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies. J Clin Invest. 2011;121(8):3109–19.PubMedPubMedCentralCrossRef Sasaki S, Sullivan M, Narvaez CF, Holmes TH, Furman D, Zheng NY, Nishtala M, Wrammert J, Smith K, James JA, et al. Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies. J Clin Invest. 2011;121(8):3109–19.PubMedPubMedCentralCrossRef
74.
go back to reference Goenka R, Scholz JL, Naradikian MS, Cancro MP. Memory B cells form in aged mice despite impaired affinity maturation and germinal center kinetics. Exp Gerontol. 2014;54:109–15.PubMedCrossRef Goenka R, Scholz JL, Naradikian MS, Cancro MP. Memory B cells form in aged mice despite impaired affinity maturation and germinal center kinetics. Exp Gerontol. 2014;54:109–15.PubMedCrossRef
75.
go back to reference Jiang N, He J, Weinstein JA, Penland L, Sasaki S, He XS, Dekker CL, Zheng NY, Huang M, Sullivan M, et al. Lineage structure of the human antibody repertoire in response to influenza vaccination. Sci Transl Med. 2013;5(171):171ra119.CrossRef Jiang N, He J, Weinstein JA, Penland L, Sasaki S, He XS, Dekker CL, Zheng NY, Huang M, Sullivan M, et al. Lineage structure of the human antibody repertoire in response to influenza vaccination. Sci Transl Med. 2013;5(171):171ra119.CrossRef
76.
go back to reference Dunn-Walters DK, Ademokun AA. B cell repertoire and ageing. Curr Opin Immunol. 2010;22(4):514–20.PubMedCrossRef Dunn-Walters DK, Ademokun AA. B cell repertoire and ageing. Curr Opin Immunol. 2010;22(4):514–20.PubMedCrossRef
77.
go back to reference Martin V, Bryan Wu YC, Kipling D, Dunn-Walters D. Ageing of the B-cell repertoire. Philos Trans R Soc B. 2015;370(1676):20140237. Martin V, Bryan Wu YC, Kipling D, Dunn-Walters D. Ageing of the B-cell repertoire. Philos Trans R Soc B. 2015;370(1676):20140237.
78.
go back to reference Ju CH, Blum LK, Kongpachith S, Lingampalli N, Mao R, Brodin P, Dekker CL, Davis MM, Robinson WH. Plasmablast antibody repertoires in elderly influenza vaccine responders exhibit restricted diversity but increased breadth of binding across influenza strains. Clin Immunol. 2018;193:70–9.PubMedPubMedCentralCrossRef Ju CH, Blum LK, Kongpachith S, Lingampalli N, Mao R, Brodin P, Dekker CL, Davis MM, Robinson WH. Plasmablast antibody repertoires in elderly influenza vaccine responders exhibit restricted diversity but increased breadth of binding across influenza strains. Clin Immunol. 2018;193:70–9.PubMedPubMedCentralCrossRef
79.
go back to reference Wang C, Liu Y, Xu LT, Jackson KJ, Roskin KM, Pham TD, Laserson J, Marshall EL, Seo K, Lee JY, et al. Effects of aging, cytomegalovirus infection, and EBV infection on human B cell repertoires. J Immunol. 2014;192(2):603–11.PubMedCrossRef Wang C, Liu Y, Xu LT, Jackson KJ, Roskin KM, Pham TD, Laserson J, Marshall EL, Seo K, Lee JY, et al. Effects of aging, cytomegalovirus infection, and EBV infection on human B cell repertoires. J Immunol. 2014;192(2):603–11.PubMedCrossRef
80.
go back to reference Henry C, Zheng NY, Huang M, Cabanov A, Rojas KT, Kaur K, Andrews SF, Palm AE, Chen YQ, Li Y, et al. Influenza virus vaccination elicits poorly adapted B cell responses in elderly individuals. Cell Host Microbe. 2019;25(3):357–66 e356.PubMedPubMedCentralCrossRef Henry C, Zheng NY, Huang M, Cabanov A, Rojas KT, Kaur K, Andrews SF, Palm AE, Chen YQ, Li Y, et al. Influenza virus vaccination elicits poorly adapted B cell responses in elderly individuals. Cell Host Microbe. 2019;25(3):357–66 e356.PubMedPubMedCentralCrossRef
81.
go back to reference Gensous N, Franceschi C, Blomberg BB, Pirazzini C, Ravaioli F, Gentilini D, Di Blasio AM, Garagnani P, Frasca D, Bacalini MG. Responders and non-responders to influenza vaccination: a DNA methylation approach on blood cells. Exp Gerontol. 2018;105:94–100.PubMedPubMedCentralCrossRef Gensous N, Franceschi C, Blomberg BB, Pirazzini C, Ravaioli F, Gentilini D, Di Blasio AM, Garagnani P, Frasca D, Bacalini MG. Responders and non-responders to influenza vaccination: a DNA methylation approach on blood cells. Exp Gerontol. 2018;105:94–100.PubMedPubMedCentralCrossRef
82.
go back to reference Colonna-Romano G, Bulati M, Aquino A, Scialabba G, Candore G, Lio D, Motta M, Malaguarnera M, Caruso C. B cells in the aged: CD27, CD5, and CD40 expression. Mech Ageing Dev. 2003;124(4):389–93.PubMedCrossRef Colonna-Romano G, Bulati M, Aquino A, Scialabba G, Candore G, Lio D, Motta M, Malaguarnera M, Caruso C. B cells in the aged: CD27, CD5, and CD40 expression. Mech Ageing Dev. 2003;124(4):389–93.PubMedCrossRef
83.
go back to reference Fang D, Cui K, Hu G, Gurram RK, Zhong C, Oler AJ, Yagi R, Zhao M, Sharma S, Liu P, et al. Bcl11b, a novel GATA3-interacting protein, suppresses Th1 while limiting Th2 cell differentiation. J Exp Med. 2018;215(5):1449–62.PubMedPubMedCentralCrossRef Fang D, Cui K, Hu G, Gurram RK, Zhong C, Oler AJ, Yagi R, Zhao M, Sharma S, Liu P, et al. Bcl11b, a novel GATA3-interacting protein, suppresses Th1 while limiting Th2 cell differentiation. J Exp Med. 2018;215(5):1449–62.PubMedPubMedCentralCrossRef
84.
go back to reference Landro L, Damas JK, Halvorsen B, Fevang B, Ueland T, Otterdal K, Heggelund L, Froland SS, Aukrust P. CXCL16 in HIV infection - a link between inflammation and viral replication. Eur J Clin Investig. 2009;39(11):1017–24.CrossRef Landro L, Damas JK, Halvorsen B, Fevang B, Ueland T, Otterdal K, Heggelund L, Froland SS, Aukrust P. CXCL16 in HIV infection - a link between inflammation and viral replication. Eur J Clin Investig. 2009;39(11):1017–24.CrossRef
85.
go back to reference Saleiro D, Kosciuczuk EM, Platanias LC. Beyond autophagy: new roles for ULK1 in immune signaling and interferon responses. Cytokine Growth Factor Rev. 2016;29:17–22.PubMedPubMedCentralCrossRef Saleiro D, Kosciuczuk EM, Platanias LC. Beyond autophagy: new roles for ULK1 in immune signaling and interferon responses. Cytokine Growth Factor Rev. 2016;29:17–22.PubMedPubMedCentralCrossRef
86.
go back to reference Zimmermann MT, Oberg AL, Grill DE, Ovsyannikova IG, Haralambieva IH, Kennedy RB, Poland GA. System-wide associations between DNA-methylation, gene expression, and Humoral immune response to influenza vaccination. PLoS One. 2016;11(3):e0152034.PubMedPubMedCentralCrossRef Zimmermann MT, Oberg AL, Grill DE, Ovsyannikova IG, Haralambieva IH, Kennedy RB, Poland GA. System-wide associations between DNA-methylation, gene expression, and Humoral immune response to influenza vaccination. PLoS One. 2016;11(3):e0152034.PubMedPubMedCentralCrossRef
87.
go back to reference Frasca D, Diaz A, Romero M, Blomberg BB. Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways. Exp Gerontol. 2017;87(Pt A):113–20.PubMedCrossRef Frasca D, Diaz A, Romero M, Blomberg BB. Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways. Exp Gerontol. 2017;87(Pt A):113–20.PubMedCrossRef
88.
go back to reference Frasca D, Diaz A, Romero M, D'Eramo F, Blomberg BB. Aging effects on T-bet expression in human B cell subsets. Cell Immunol. 2017;321:68–73.PubMedCrossRef Frasca D, Diaz A, Romero M, D'Eramo F, Blomberg BB. Aging effects on T-bet expression in human B cell subsets. Cell Immunol. 2017;321:68–73.PubMedCrossRef
89.
go back to reference Claes N, Fraussen J, Vanheusden M, Hellings N, Stinissen P, Van Wijmeersch B, Hupperts R, Somers V. Age-associated B cells with Proinflammatory characteristics are expanded in a proportion of multiple sclerosis patients. J Immunol. 2016;197(12):4576–83.PubMedCrossRef Claes N, Fraussen J, Vanheusden M, Hellings N, Stinissen P, Van Wijmeersch B, Hupperts R, Somers V. Age-associated B cells with Proinflammatory characteristics are expanded in a proportion of multiple sclerosis patients. J Immunol. 2016;197(12):4576–83.PubMedCrossRef
90.
go back to reference Colonna-Romano G, Bulati M, Aquino A, Pellicano M, Vitello S, Lio D, Candore G, Caruso C. A double-negative (IgD-CD27-) B cell population is increased in the peripheral blood of elderly people. Mech Ageing Dev. 2009;130(10):681–90.PubMedCrossRef Colonna-Romano G, Bulati M, Aquino A, Pellicano M, Vitello S, Lio D, Candore G, Caruso C. A double-negative (IgD-CD27-) B cell population is increased in the peripheral blood of elderly people. Mech Ageing Dev. 2009;130(10):681–90.PubMedCrossRef
91.
go back to reference Adlowitz DG, Barnard J, Biear JN, Cistrone C, Owen T, Wang W, Palanichamy A, Ezealah E, Campbell D, Wei C, et al. Expansion of activated peripheral blood memory B cells in rheumatoid arthritis, impact of B cell depletion therapy, and biomarkers of response. PLoS One. 2015;10(6):e0128269.PubMedPubMedCentralCrossRef Adlowitz DG, Barnard J, Biear JN, Cistrone C, Owen T, Wang W, Palanichamy A, Ezealah E, Campbell D, Wei C, et al. Expansion of activated peripheral blood memory B cells in rheumatoid arthritis, impact of B cell depletion therapy, and biomarkers of response. PLoS One. 2015;10(6):e0128269.PubMedPubMedCentralCrossRef
92.
go back to reference Wehr C, Eibel H, Masilamani M, Illges H, Schlesier M, Peter HH, Warnatz K. A new CD21low B cell population in the peripheral blood of patients with SLE. Clin Immunol. 2004;113(2):161–71.PubMedCrossRef Wehr C, Eibel H, Masilamani M, Illges H, Schlesier M, Peter HH, Warnatz K. A new CD21low B cell population in the peripheral blood of patients with SLE. Clin Immunol. 2004;113(2):161–71.PubMedCrossRef
93.
go back to reference Chang LY, Li Y, Kaplan DE. Hepatitis C viraemia reversibly maintains subset of antigen-specific T-bet+ tissue-like memory B cells. J Viral Hepat. 2016. Chang LY, Li Y, Kaplan DE. Hepatitis C viraemia reversibly maintains subset of antigen-specific T-bet+ tissue-like memory B cells. J Viral Hepat. 2016.
94.
go back to reference Illingworth J, Butler NS, Roetynck S, Mwacharo J, Pierce SK, Bejon P, Crompton PD, Marsh K, Ndungu FM. Chronic exposure to plasmodium falciparum is associated with phenotypic evidence of B and T cell exhaustion. J Immunol. 2013;190(3):1038–47.PubMedCrossRef Illingworth J, Butler NS, Roetynck S, Mwacharo J, Pierce SK, Bejon P, Crompton PD, Marsh K, Ndungu FM. Chronic exposure to plasmodium falciparum is associated with phenotypic evidence of B and T cell exhaustion. J Immunol. 2013;190(3):1038–47.PubMedCrossRef
95.
go back to reference Moir S, Ho J, Malaspina A, Wang W, DiPoto AC, O'Shea MA, Roby G, Kottilil S, Arthos J, Proschan MA, et al. Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J Exp Med. 2008;205(8):1797–805.PubMedPubMedCentralCrossRef Moir S, Ho J, Malaspina A, Wang W, DiPoto AC, O'Shea MA, Roby G, Kottilil S, Arthos J, Proschan MA, et al. Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J Exp Med. 2008;205(8):1797–805.PubMedPubMedCentralCrossRef
96.
go back to reference Hao Y, O'Neill P, Naradikian MS, Scholz JL, Cancro MP. A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice. Blood. 2011;118(5):1294–304.PubMedPubMedCentralCrossRef Hao Y, O'Neill P, Naradikian MS, Scholz JL, Cancro MP. A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice. Blood. 2011;118(5):1294–304.PubMedPubMedCentralCrossRef
97.
go back to reference Rubtsov AV, Rubtsova K, Fischer A, Meehan RT, Gillis JZ, Kappler JW, Marrack P. Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c(+) B-cell population is important for the development of autoimmunity. Blood. 2011;118(5):1305–15.PubMedPubMedCentralCrossRef Rubtsov AV, Rubtsova K, Fischer A, Meehan RT, Gillis JZ, Kappler JW, Marrack P. Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c(+) B-cell population is important for the development of autoimmunity. Blood. 2011;118(5):1305–15.PubMedPubMedCentralCrossRef
98.
go back to reference Naradikian MS, Myles A, Beiting DP, Roberts KJ, Dawson L, Herati RS, Bengsch B, Linderman SL, Stelekati E, Spolski R, et al. Cutting edge: IL-4, IL-21, and IFN-gamma interact to govern T-bet and CD11c expression in TLR-activated B cells. J Immunol. 2016;197(4):1023–8.PubMedCrossRef Naradikian MS, Myles A, Beiting DP, Roberts KJ, Dawson L, Herati RS, Bengsch B, Linderman SL, Stelekati E, Spolski R, et al. Cutting edge: IL-4, IL-21, and IFN-gamma interact to govern T-bet and CD11c expression in TLR-activated B cells. J Immunol. 2016;197(4):1023–8.PubMedCrossRef
99.
go back to reference Russell Knode LM, Naradikian MS, Myles A, Scholz JL, Hao Y, Liu D, Ford ML, Tobias JW, Cancro MP, Gearhart PJ. Age-associated B cells express a diverse repertoire of VH and Vkappa genes with somatic Hypermutation. J Immunol. 2017;198(5):1921–7.PubMedCrossRef Russell Knode LM, Naradikian MS, Myles A, Scholz JL, Hao Y, Liu D, Ford ML, Tobias JW, Cancro MP, Gearhart PJ. Age-associated B cells express a diverse repertoire of VH and Vkappa genes with somatic Hypermutation. J Immunol. 2017;198(5):1921–7.PubMedCrossRef
100.
go back to reference Johnson JL, Rosenthal RL, Knox JJ, Myles A, Naradikian MS, Madej J, Kostiv M, Rosenfeld AM, Meng W, Christensen SR, et al. The transcription factor T-bet resolves memory B cell subsets with distinct tissue distributions and antibody specificities in mice and humans. Immunity. 2020;52(5):842–55 e846.PubMedCrossRefPubMedCentral Johnson JL, Rosenthal RL, Knox JJ, Myles A, Naradikian MS, Madej J, Kostiv M, Rosenfeld AM, Meng W, Christensen SR, et al. The transcription factor T-bet resolves memory B cell subsets with distinct tissue distributions and antibody specificities in mice and humans. Immunity. 2020;52(5):842–55 e846.PubMedCrossRefPubMedCentral
101.
go back to reference Swain SL, Kugler-Umana O, Kuang Y, Zhang W. The properties of the unique age-associated B cell subset reveal a shift in strategy of immune response with age. Cell Immunol. 2017;321:52–60.PubMedPubMedCentralCrossRef Swain SL, Kugler-Umana O, Kuang Y, Zhang W. The properties of the unique age-associated B cell subset reveal a shift in strategy of immune response with age. Cell Immunol. 2017;321:52–60.PubMedPubMedCentralCrossRef
102.
go back to reference Tchkonia T, Morbeck DE, Von Zglinicki T, Van Deursen J, Lustgarten J, Scrable H, Khosla S, Jensen MD, Kirkland JL. Fat tissue, aging, and cellular senescence. Aging Cell. 2010;9(5):667–84.PubMedCrossRef Tchkonia T, Morbeck DE, Von Zglinicki T, Van Deursen J, Lustgarten J, Scrable H, Khosla S, Jensen MD, Kirkland JL. Fat tissue, aging, and cellular senescence. Aging Cell. 2010;9(5):667–84.PubMedCrossRef
103.
go back to reference Zamboni M, Rossi AP, Fantin F, Zamboni G, Chirumbolo S, Zoico E, Mazzali G. Adipose tissue, diet and aging. Mech Ageing Dev. 2014;136–137:129–37.PubMedCrossRef Zamboni M, Rossi AP, Fantin F, Zamboni G, Chirumbolo S, Zoico E, Mazzali G. Adipose tissue, diet and aging. Mech Ageing Dev. 2014;136–137:129–37.PubMedCrossRef
104.
go back to reference Foster MC, Hwang SJ, Porter SA, Massaro JM, Hoffmann U, Fox CS. Fatty kidney, hypertension, and chronic kidney disease: the Framingham heart study. Hypertension. 2011;58(5):784–90.PubMedCrossRef Foster MC, Hwang SJ, Porter SA, Massaro JM, Hoffmann U, Fox CS. Fatty kidney, hypertension, and chronic kidney disease: the Framingham heart study. Hypertension. 2011;58(5):784–90.PubMedCrossRef
105.
go back to reference Machann J, Thamer C, Schnoedt B, Stefan N, Stumvoll M, Haring HU, Claussen CD, Fritsche A, Schick F. Age and gender related effects on adipose tissue compartments of subjects with increased risk for type 2 diabetes: a whole body MRI/MRS study. MAGMA. 2005;18(3):128–37.PubMedCrossRef Machann J, Thamer C, Schnoedt B, Stefan N, Stumvoll M, Haring HU, Claussen CD, Fritsche A, Schick F. Age and gender related effects on adipose tissue compartments of subjects with increased risk for type 2 diabetes: a whole body MRI/MRS study. MAGMA. 2005;18(3):128–37.PubMedCrossRef
106.
go back to reference Ryan AS, Nicklas BJ. Age-related changes in fat deposition in mid-thigh muscle in women: relationships with metabolic cardiovascular disease risk factors. Int J Obes Relat Metab Disord. 1999;23(2):126–32.PubMedCrossRef Ryan AS, Nicklas BJ. Age-related changes in fat deposition in mid-thigh muscle in women: relationships with metabolic cardiovascular disease risk factors. Int J Obes Relat Metab Disord. 1999;23(2):126–32.PubMedCrossRef
107.
go back to reference Saisho Y, Butler AE, Meier JJ, Monchamp T, Allen-Auerbach M, Rizza RA, Butler PC. Pancreas volumes in humans from birth to age one hundred taking into account sex, obesity, and presence of type-2 diabetes. Clin Anat. 2007;20(8):933–42.PubMedPubMedCentralCrossRef Saisho Y, Butler AE, Meier JJ, Monchamp T, Allen-Auerbach M, Rizza RA, Butler PC. Pancreas volumes in humans from birth to age one hundred taking into account sex, obesity, and presence of type-2 diabetes. Clin Anat. 2007;20(8):933–42.PubMedPubMedCentralCrossRef
108.
go back to reference Silaghi A, Piercecchi-Marti MD, Grino M, Leonetti G, Alessi MC, Clement K, Dadoun F, Dutour A. Epicardial adipose tissue extent: relationship with age, body fat distribution, and coronaropathy. Obesity (Silver Spring). 2008;16(11):2424–30.CrossRef Silaghi A, Piercecchi-Marti MD, Grino M, Leonetti G, Alessi MC, Clement K, Dadoun F, Dutour A. Epicardial adipose tissue extent: relationship with age, body fat distribution, and coronaropathy. Obesity (Silver Spring). 2008;16(11):2424–30.CrossRef
109.
110.
go back to reference Najarro K, Nguyen H, Chen G, Xu M, Alcorta S, Yao X, Zukley L, Metter EJ, Truong T, Lin Y, et al. Telomere length as an Indicator of the robustness of B- and T-cell response to influenza in older adults. J Infect Dis. 2015;212(8):1261–9.PubMedPubMedCentralCrossRef Najarro K, Nguyen H, Chen G, Xu M, Alcorta S, Yao X, Zukley L, Metter EJ, Truong T, Lin Y, et al. Telomere length as an Indicator of the robustness of B- and T-cell response to influenza in older adults. J Infect Dis. 2015;212(8):1261–9.PubMedPubMedCentralCrossRef
Metadata
Title
Aging induces B cell defects and decreased antibody responses to influenza infection and vaccination
Authors
Daniela Frasca
Bonnie B. Blomberg
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2020
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/s12979-020-00210-z

Other articles of this Issue 1/2020

Immunity & Ageing 1/2020 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.