Top

Published in:

01-05-2014 | Review

Plasma cells in immunopathology: concepts and therapeutic strategies

Authors: Benjamin Tiburzy, Upasana Kulkarni, Anja Erika Hauser, Melanie Abram, Rudolf Armin Manz

Published in: Seminars in Immunopathology | Issue 3/2014

Abstract

Plasma cells are terminally differentiated B cells that secrete antibodies, important for immune protection, but also contribute to any allergic and autoimmune disease. There is increasing evidence that plasma cell populations exhibit a considerable degree of heterogeneity with respect to their immunophenotype, migration behavior, lifetime, and susceptibility to immunosuppressive drugs. Pathogenic long-lived plasma cells are refractory to existing therapies. In contrast, short-lived plasma cells can be depleted by steroids and cytostatic drugs. Therefore, long-lived plasma cells are responsible for therapy-resistant autoantibodies and resemble a challenge for the therapy of antibody-mediated autoimmune diseases. Both lifetime and therapy resistance of plasma cells are supported by factors produced within their microenviromental niches. Current results suggest that plasma cell differentiation and survival factors such as IL-6 also signal via mammalian miRNAs within the plasma cell to modulate downstream transcription factors. Recent evidence also suggests that plasma cells and/or their immediate precursors (plasmablasts) can produce important cytokines and act as antigen-presenting cells, exhibiting so far underestimated roles in immune regulation and bone homeostasis. Here, we provide an overview on plasma cell biology and discuss exciting, experimental, and potential therapeutic approaches to eliminate pathogenic plasma cells.

Miller FR (1931) The induced development and histogenesis of plasma cells. J Exp Med 54:333–347PubMedCentralPubMed

Ehrich WE, Drabkin DL, Forman C (1949) Nucleic acids and the production of antibody by plasma cells. J Exp Med 90:157–168PubMedCentralPubMed

Manz RA, Hauser AE, Hiepe F, Radbruch A (2005) Maintenance of serum antibody levels. Annu Rev Immunol 23:367–386. doi:10.1146/annurev.immunol.23.021704.115723 PubMed

Manz RA, Thiel A, Radbruch A (1997) Lifetime of plasma cells in the bone marrow. Nature 388:133–134. doi:10.1038/40540 PubMed

Slifka MK, Antia R, Whitmire JK, Ahmed R (1998) Humoral immunity due to long-lived plasma cells. Immunity 8:363–372PubMed

Hoyer BF (2004) Short-lived plasmablasts and long-lived plasma cells contribute to chronic humoral autoimmunity in NZB/W mice. J Exp Med 199:1577–1584. doi:10.1084/jem.20040168 PubMedCentralPubMed

Mumtaz IM, Hoyer BF, Panne D et al (2012) Bone marrow of NZB/W mice is the major site for plasma cells resistant to dexamethasone and cyclophosphamide: implications for the treatment of autoimmunity. J Autoimmun 39:180–188. doi:10.1016/j.jaut.2012.05.010 PubMed

Ferraro AJ, Drayson MT, Savage COS, MacLennan ICM (2008) Levels of autoantibodies, unlike antibodies to all extrinsic antigen groups, fall following B cell depletion with rituximab. Eur J Immunol 38:292–298. doi:10.1002/eji.200737557 PubMed

Luger EO, Fokuhl V, Wegmann M et al (2009) Induction of long-lived allergen-specific plasma cells by mucosal allergen challenge. J Allergy Clin Immunol 124:819–826.e4. doi:10.1016/j.jaci.2009.06.047 PubMed

10.

Cassese G, Arce S, Hauser AE et al (2003) Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals. J Immunol 171:1684–1690PubMed

11.

Winter O, Moser K, Mohr E et al (2010) Megakaryocytes constitute a functional component of a plasma cell niche in the bone marrow. Blood 116:1867–1875. doi:10.1182/blood-2009-12-259457 PubMed

12.

Chu VT, Fröhlich A, Steinhauser G et al (2011) Eosinophils are required for the maintenance of plasma cells in the bone marrow. Nat Immunol 12:151–159. doi:10.1038/ni.1981 PubMed

13.

Matthes T, Werner-Favre C, Zubler RH (1995) Cytokine expression and regulation of human plasma cells: disappearance of interleukin-10 and persistence of transforming growth factor-beta 1. Eur J Immunol 25:508–512. doi:10.1002/eji.1830250230 PubMed

14.

Li Y, Toraldo G, Li A et al (2007) B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo. Blood 109:3839–3848. doi:10.1182/blood-2006-07-037994 PubMedCentralPubMed

15.

Madan R, Demircik F, Surianarayanan S et al (2009) Nonredundant roles for B cell-derived IL-10 in immune counter-regulation. J Immunol 183:2312–2320. doi:10.4049/jimmunol.0900185 PubMedCentralPubMed

16.

Maseda D, Smith SH, DiLillo DJ et al (2012) Regulatory B10 cells differentiate into antibody-secreting cells after transient IL-10 production in vivo. J Immunol 188:1036–1048. doi:10.4049/jimmunol.1102500 PubMedCentralPubMed

17.

Bermejo DA, Jackson SW, Gorosito-Serran M et al (2013) Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORγt and Ahr that leads to IL-17 production by activated B cells. Nat Immunol 14:514–522. doi:10.1038/ni.2569 PubMedCentralPubMed

18.

Pelletier N, McHeyzer-Williams LJ, Wong KA et al (2010) Plasma cells negatively regulate the follicular helper T cell program. Nat Immunol 11:1110–1118. doi:10.1038/ni.1954 PubMedCentralPubMed

19.

Kunkel EJ, Campbell DJ, Butcher EC (2003) Chemokines in lymphocyte trafficking and intestinal immunity. Microcirculation 10:313–323. doi:10.1038/sj.mn.7800196 PubMed

20.

Moser K, Tokoyoda K, Radbruch A et al (2006) Stromal niches, plasma cell differentiation and survival. Curr Opin Immunol 18:265–270. doi:10.1016/j.coi.2006.03.004 PubMed

21.

Kabashima K, Haynes NM, Xu Y et al (2006) Plasma cell S1P1 expression determines secondary lymphoid organ retention versus bone marrow tropism. J Exp Med 203:2683–2690. doi:10.1084/jem.20061289 PubMedCentralPubMed

22.

Odendahl M, Mei H, Hoyer BF et al (2005) Generation of migratory antigen-specific plasma blasts and mobilization of resident plasma cells in a secondary immune response. Blood 105:1614–1621. doi:10.1182/blood-2004-07-2507 PubMed

23.

DiLillo DJ, Hamaguchi Y, Ueda Y et al (2008) Maintenance of long-lived plasma cells and serological memory despite mature and memory B cell depletion during CD20 immunotherapy in mice. J Immunol 180:361–371PubMed

24.

Muehlinghaus G, Cigliano L, Huehn S et al (2005) Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells. Blood 105:3965–3971. doi:10.1182/blood-2004-08-2992 PubMed

25.

Moser K, Kalies K, Szyska M et al (2012) CXCR3 promotes the production of IgG1 autoantibodies but is not essential for the development of lupus nephritis in NZB/NZW mice. Arthritis Rheum 64:1237–1246. doi:10.1002/art.33424 PubMed

26.

Lacotte S, Decossas M, Le Coz C et al (2013) Early differentiated CD138(high) MHCII + IgG + plasma cells express CXCR3 and localize into inflamed kidneys of lupus mice. PLoS ONE 8:e58140. doi:10.1371/journal.pone.0058140 PubMedCentralPubMed

27.

Panzer U, Steinmetz OM, Paust H-J et al (2007) Chemokine receptor CXCR3 mediates T cell recruitment and tissue injury in nephrotoxic nephritis in mice. J Am Soc Nephrol 18:2071–2084. doi:10.1681/ASN.2006111237 PubMed

28.

Espeli M, Bökers S, Giannico G et al (2011) Local renal autoantibody production in lupus nephritis. J Am Soc Nephrol 22:296–305. doi:10.1681/ASN.2010050515 PubMedCentralPubMed

29.

Noris M, Bernasconi S, Casiraghi F et al (1995) Monocyte chemoattractant protein-1 is excreted in excessive amounts in the urine of patients with lupus nephritis. Lab Investig 73:804–809PubMed

30.

Amoura Z, Combadiere C, Faure S et al (2003) Roles of CCR2 and CXCR3 in the T cell-mediated response occurring during lupus flares. Arthritis Rheum 48:3487–3496. doi:10.1002/art.11350 PubMed

31.

Rafei M, Hsieh J, Fortier S et al (2008) Mesenchymal stromal cell-derived CCL2 suppresses plasma cell immunoglobulin production via STAT3 inactivation and PAX5 induction. Blood 112:4991–4998. doi:10.1182/blood-2008-07-166892 PubMed

32.

Mei HE, Yoshida T, Sime W et al (2009) Blood-borne human plasma cells in steady state are derived from mucosal immune responses. Blood 113:2461–2469. doi:10.1182/blood-2008-04-153544 PubMed

33.

Kantele A, Kantele JM, Savilahti E et al (1997) Homing potentials of circulating lymphocytes in humans depend on the site of activation: oral, but not parenteral, typhoid vaccination induces circulating antibody-secreting cells that all bear homing receptors directing them to the gut. J Immunol 158:574–579PubMed

34.

Medina F, Segundo C, Campos-Caro A et al (2002) The heterogeneity shown by human plasma cells from tonsil, blood, and bone marrow reveals graded stages of increasing maturity, but local profiles of adhesion molecule expression. Blood 99:2154–2161PubMed

35.

Arce S, Luger E, Muehlinghaus G et al (2004) CD38 low IgG-secreting cells are precursors of various CD38 high-expressing plasma cell populations. J Leukoc Biol 75:1022–1028. doi:10.1189/jlb.0603279 PubMed

36.

Ellyard JI, Avery DT, Phan TG et al (2004) Antigen-selected, immunoglobulin-secreting cells persist in human spleen and bone marrow. Blood 103:3805–3812. doi:10.1182/blood-2003-09-3109 PubMed

37.

Kunisawa J, Gohda M, Hashimoto E et al (2013) Microbe-dependent CD11b⁺ IgA⁺ plasma cells mediate robust early-phase intestinal IgA responses in mice. Nat Commun 4:1772. doi:10.1038/ncomms2718 PubMedCentralPubMed

38.

Hiepe F, Dörner T, Hauser AE et al (2011) Long-lived autoreactive plasma cells drive persistent autoimmune inflammation. Nat Rev Rheumatol 7:170–178. doi:10.1038/nrrheum.2011.1 PubMed

39.

Starke C, Frey S, Wellmann U et al (2011) High frequency of autoantibody-secreting cells and long-lived plasma cells within inflamed kidneys of NZB/W F1 lupus mice. Eur J Immunol 41:2107–2112. doi:10.1002/eji.201041315 PubMed

40.

Pachner AR, Li L, Lagunoff D (2011) Plasma cells in the central nervous system in the Theiler’s virus model of multiple sclerosis. J Neuroimmunol 232:35–40. doi:10.1016/j.jneuroim.2010.09.026 PubMed

41.

Szyszko EA, Brokstad KA, Oijordsbakken G et al (2011) Salivary glands of primary Sjögren’s syndrome patients express factors vital for plasma cell survival. Arthritis Res Ther 13:R2. doi:10.1186/ar3220 PubMedCentralPubMed

42.

Doorenspleet ME, Klarenbeek PL, de Hair MJH et al (2013) Rheumatoid arthritis synovial tissue harbours dominant B-cell and plasma-cell clones associated with autoreactivity. Ann Rheum Dis. doi:10.1136/annrheumdis-2012-202861 PubMed

43.

Ho F, Lortan JE, MacLennan IC, Khan M (1986) Distinct short-lived and long-lived antibody-producing cell populations. Eur J Immunol 16:1297–1301. doi:10.1002/eji.1830161018 PubMed

44.

Belnoue E, Pihlgren M, McGaha TL et al (2008) APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells. Blood 111:2755–2764. doi:10.1182/blood-2007-09-110858 PubMed

45.

Mohr E, Serre K, Manz RA et al (2009) Dendritic cells and monocyte/macrophages that create the IL-6/APRIL-rich lymph node microenvironments where plasmablasts mature. J Immunol 182:2113PubMed

46.

Winter O, Mohr E, Manz RA (2011) Alternative cell types form a multi-component-plasma-cell-niche. Immunol Lett 141:145–146. doi:10.1016/j.imlet.2011.07.006 PubMed

47.

Corsiero E, Bombardieri M, Manzo A et al (2012) Role of lymphoid chemokines in the development of functional ectopic lymphoid structures in rheumatic autoimmune diseases. Immunol Lett 145:62–67. doi:10.1016/j.imlet.2012.04.013 PubMed

48.

Gabay C, Krenn V, Bosshard C et al (2009) Synovial tissues concentrate secreted APRIL. Arthritis Res Ther 11:R144. doi:10.1186/ar2817 PubMedCentralPubMed

49.

Macpherson AJ, Gatto D, Sainsbury E et al (2000) A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science 288:2222–2226PubMed

50.

Diana J, Moura IC, Vaugier C et al (2013) Secretory IgA induces tolerogenic dendritic cells through SIGNR1 dampening autoimmunity in mice. J Immunol 191:2335–2343. doi:10.4049/jimmunol.1300864 PubMed

51.

Di Niro R, Mesin L, Zheng N-Y et al (2012) High abundance of plasma cells secreting transglutaminase 2-specific IgA autoantibodies with limited somatic hypermutation in celiac disease intestinal lesions. Nat Med 18:441–445. doi:10.1038/nm.2656 PubMed

52.

Ludwig RJ, Recke A, Bieber K et al (2011) Generation of antibodies of distinct subclasses and specificity is linked to H2s in an active mouse model of epidermolysis bullosa acquisita. J Invest Dermatol 131:167–176. doi:10.1038/jid.2010.248 PubMed

53.

Cerutti A, Rescigno M (2008) The biology of intestinal immunoglobulin A responses. Immunity 28:740–750. doi:10.1016/j.immuni.2008.05.001 PubMedCentralPubMed

54.

Fagarasan S, Kinoshita K, Muramatsu M et al (2001) In situ class switching and differentiation to IgA-producing cells in the gut lamina propria. Nature 413:639–643. doi:10.1038/35098100 PubMed

55.

Fritz JH, Rojas OL, Simard N et al (2012) Acquisition of a multifunctional IgA + plasma cell phenotype in the gut. Nature 481:199–203. doi:10.1038/nature10698

56.

Lindner C, Wahl B, Föhse L et al (2012) Age, microbiota, and T cells shape diverse individual IgA repertoires in the intestine. J Exp Med 209:365–377. doi:10.1084/jem.20111980 PubMedCentralPubMed

57.

Benckert J, Schmolka N, Kreschel C et al (2011) The majority of intestinal IgA + and IgG + plasmablasts in the human gut are antigen-specific. J Clin Invest 121:1946–1955. doi:10.1172/JCI44447 PubMedCentralPubMed

58.

Hapfelmeier S, Lawson MAE, Slack E et al (2010) Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science 328:1705–1709. doi:10.1126/science.1188454 PubMedCentralPubMed

59.

Mesin L, Di Niro R, Thompson KM et al (2011) Long-lived plasma cells from human small intestine biopsies secrete immunoglobulins for many weeks in vitro. J Immunol 187:2867–2874. doi:10.4049/jimmunol.1003181 PubMed

60.

Youngman KR, Franco MA, Kuklin NA et al (2002) Correlation of tissue distribution, developmental phenotype, and intestinal homing receptor expression of antigen-specific B cells during the murine anti-rotavirus immune response. J Immunol 168:2173–2181PubMed

61.

Manz RA, Arce S, Cassese G et al (2002) Humoral immunity and long-lived plasma cells. Curr Opin Immunol 14:517–521PubMed

62.

Yoshida T, Mei H, Dörner T et al (2010) Memory B and memory plasma cells. Immunol Rev 237:117–139. doi:10.1111/j.1600-065X.2010.00938.x PubMed

63.

Neubert K, Meister S, Moser K et al (2008) The proteasome inhibitor bortezomib depletes plasma cells and protects mice with lupus-like disease from nephritis. Nat Med 14:748–755. doi:10.1038/nm1763 PubMed

64.

Bontscho J, Schreiber A, Manz RA et al (2011) Myeloperoxidase-specific plasma cell depletion by bortezomib protects from anti-neutrophil cytoplasmic autoantibodies-induced glomerulonephritis. J Am Soc Nephrol 22:336–348. doi:10.1681/ASN.2010010034 PubMedCentralPubMed

65.

Gomez AM, Vrolix K, Martínez-Martínez P et al (2011) Proteasome inhibition with bortezomib depletes plasma cells and autoantibodies in experimental autoimmune myasthenia gravis. J Immunol 186:2503–2513. doi:10.4049/jimmunol.1002539 PubMed

66.

Kasperkiewicz M, Müller R, Manz R et al (2011) Heat-shock protein 90 inhibition in autoimmunity to type VII collagen: evidence that nonmalignant plasma cells are not therapeutic targets. Blood 117:6135PubMed

67.

Mei HE, Schmidt S, Dörner T (2012) Rationale of anti-CD19 immunotherapy: an option to target autoreactive plasma cells in autoimmunity. Arthritis Res Ther 14(Suppl 5):S1. doi:10.1186/ar3909 PubMedCentralPubMed

68.

O’Connor BP, Raman VS, Erickson LD et al (2004) BCMA is essential for the survival of long-lived bone marrow plasma cells. J Exp Med 199:91–98. doi:10.1084/jem.20031330 PubMedCentralPubMed

69.

Baltimore D, Boldin MP, O’Connell RM et al (2008) MicroRNAs: new regulators of immune cell development and function. Nat Immunol 9:839–845. doi:10.1038/ni.f.209 PubMed

70.

Georgantas RW 3rd, Hildreth R, Morisot S et al (2007) CD34+ hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control. Proc Natl Acad Sci U S A 104:2750–2755. doi:10.1073/pnas.0610983104 PubMedCentralPubMed

71.

Rodriguez A, Vigorito E, Clare S et al (2007) Requirement of bic/microRNA-155 for normal immune function. Science 316:608–611. doi:10.1126/science.1139253 PubMedCentralPubMed

72.

Vigorito E, Perks KL, Abreu-Goodger C et al (2007) microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity 27:847–859. doi:10.1016/j.immuni.2007.10.009 PubMedCentralPubMed

73.

Teng G, Hakimpour P, Landgraf P et al (2008) MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase. Immunity 28:621–629. doi:10.1016/j.immuni.2008.03.015 PubMedCentralPubMed

74.

Dorsett Y, McBride KM, Jankovic M et al (2008) MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation. Immunity 28:630–638. doi:10.1016/j.immuni.2008.04.002 PubMedCentralPubMed

75.

Dagan LN, Jiang X, Bhatt S et al (2012) miR-155 regulates HGAL expression and increases lymphoma cell motility. Blood 119:513–520. doi:10.1182/blood-2011-08-370536 PubMedCentralPubMed

76.

Gururajan M, Haga CL, Das S et al (2010) MicroRNA 125b inhibition of B cell differentiation in germinal centers. Int Immunol 22:583–592. doi:10.1093/intimm/dxq042 PubMedCentralPubMed

77.

Gabler J, Wittmann J, Porstner M et al (2013) Contribution of microRNA 24-3p and Erk1/2 to interleukin-6-mediated plasma cell survival. Eur J Immunol. doi:10.1002/eji.201243271 PubMed

78.

Iborra M, Bernuzzi F, Invernizzi P, Danese S (2012) MicroRNAs in autoimmunity and inflammatory bowel disease: crucial regulators in immune response. Autoimmun Rev 11:305–314. doi:10.1016/j.autrev.2010.07.002 PubMed

79.

Pichiorri F, Suh S-S, Ladetto M et al (2008) MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis. Proc Natl Acad Sci U S A 105:12885–12890. doi:10.1073/pnas.0806202105 PubMedCentralPubMed

80.

Löffler D, Brocke-Heidrich K, Pfeifer G et al (2007) Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood 110:1330–1333. doi:10.1182/blood-2007-03-081133 PubMed

81.

O’Donnell KA, Wentzel EA, Zeller KI et al (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435:839–843. doi:10.1038/nature03677 PubMed

82.

Xiao C, Srinivasan L, Calado DP et al (2008) Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol 9:405–414. doi:10.1038/ni1575 PubMedCentralPubMed

83.

Pichiorri F, Suh S-S, Rocci A et al (2010) Downregulation of p53-inducible microRNAs 192, 194, and 215 impairs the p53/MDM2 autoregulatory loop in multiple myeloma development. Cancer Cell 18:367–381. doi:10.1016/j.ccr.2010.09.005 PubMedCentralPubMed

84.

Belver L, de Yébenes VG, Ramiro AR (2010) MicroRNAs prevent the generation of autoreactive antibodies. Immunity 33:713–722. doi:10.1016/j.immuni.2010.11.010 PubMedCentralPubMed

85.

Boldin MP, Taganov KD, Rao DS et al (2011) miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J Exp Med 208:1189–1201. doi:10.1084/jem.20101823 PubMedCentralPubMed

86.

Stanczyk J, Pedrioli DML, Brentano F et al (2008) Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum 58:1001–1009. doi:10.1002/art.23386 PubMed

87.

Nakasa T, Miyaki S, Okubo A et al (2008) Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum 58:1284–1292. doi:10.1002/art.23429 PubMedCentralPubMed

88.

Tang Y, Luo X, Cui H et al (2009) MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum 60:1065–1075. doi:10.1002/art.24436 PubMed

89.

Krützfeldt J, Rajewsky N, Braich R et al (2005) Silencing of microRNAs in vivo with “antagomirs”. Nature 438:685–689PubMed

90.

Gao X, Zhang R, Qu X et al (2012) MiR-15a, miR-16-1 and miR-17-92 cluster expression are linked to poor prognosis in multiple myeloma. Leuk Res 36:1505–1509. doi:10.1016/j.leukres.2012.08.021 PubMed

91.

Fillatreau S (2013) Cytokine-producing B cells as regulators of pathogenic and protective immune responses. Ann Rheum Dis 72(Suppl 2):ii80–ii84. doi:10.1136/annrheumdis-2012-202253 PubMed

92.

Barr TA, Shen P, Brown S et al (2012) B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6-producing B cells. J Exp Med 209:1001–1010. doi:10.1084/jem.20111675 PubMedCentralPubMed

93.

Sugimoto K, Ogawa A, Shimomura Y et al (2007) Inducible IL-12-producing B cells regulate Th2-mediated intestinal inflammation. Gastroenterology 133:124–136. doi:10.1053/j.gastro.2007.03.112 PubMed

94.

Mizoguchi A, Bhan AK (2006) A case for regulatory B cells. J Immunol 176:705–710PubMed

95.

Moore KW, de Waal MR, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765. doi:10.1146/annurev.immunol.19.1.683 PubMed

96.

Fillatreau S, Sweenie CH, McGeachy MJ et al (2002) B cells regulate autoimmunity by provision of IL-10. Nat Immunol 3:944–950. doi:10.1038/ni833 PubMed

97.

Iwata Y, Matsushita T, Horikawa M et al (2011) Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 117:530–541. doi:10.1182/blood-2010-07-294249 PubMedCentralPubMed

98.

Vitale G, Mion F, Pucillo C (2010) Regulatory B cells: evidence, developmental origin and population diversity. Mol Immunol 48:1–8. doi:10.1016/j.molimm.2010.09.010 PubMed

99.

Rafei M, Hsieh J, Zehntner S et al (2009) A granulocyte-macrophage colony-stimulating factor and interleukin-15 fusokine induces a regulatory B cell population with immune suppressive properties. Nat Med 15:1038–1045. doi:10.1038/nm.2003 PubMed

100.

Neves P, Lampropoulou V, Calderon-Gomez E et al (2010) Signaling via the MyD88 adaptor protein in B cells suppresses protective immunity during Salmonella typhimurium infection. Immunity 33:777–790. doi:10.1016/j.immuni.2010.10.016 PubMed

101.

Scapini P, Lamagna C, Hu Y et al (2011) B cell-derived IL-10 suppresses inflammatory disease in Lyn-deficient mice. Proc Natl Acad Sci U S A 108:E823–E832. doi:10.1073/pnas.1107913108 PubMedCentralPubMed

102.

Otsuki T, Yata K, Sakaguchi H et al (2002) IL-10 in myeloma cells. Leuk Lymphoma 43:969–974PubMed

103.

Yoshimura A, Muto G (2011) TGF-β function in immune suppression. Curr Top Microbiol Immunol 350:127–147. doi:10.1007/82_2010_87 PubMed

104.

Fazilleau N, Mark L, McHeyzer-Williams LJ, McHeyzer-Williams MG (2009) Follicular helper T cells: lineage and location. Immunity 30:324–335. doi:10.1016/j.immuni.2009.03.003 PubMedCentralPubMed

Title: Plasma cells in immunopathology: concepts and therapeutic strategies
Authors: Benjamin Tiburzy
Upasana Kulkarni
Anja Erika Hauser
Melanie Abram
Rudolf Armin Manz
Publication date: 01-05-2014
Publisher: Springer Berlin Heidelberg
Published in: Seminars in Immunopathology / Issue 3/2014
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-014-0426-8

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

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

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2014

The pathogenesis and diagnosis of systemic lupus erythematosus: still not resolved

Rationale for B cell targeting in SLE

Targeting B cells and autoantibodies in the therapy of autoimmune diseases

Introduction: B cell-mediated autoimmune diseases

The pathogenic potential of autoreactive antibodies in rheumatoid arthritis

B cell-mediated pathogenesis of ANCA-mediated vasculitis

Keynote webinar | Spotlight on medication adherence

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

At a glance: The STEP trials