Top

Published in:

01-07-2008

Anti-Sm B cell tolerance and tolerance loss in systemic lupus erythematosus

Author: Stephen H. Clarke

Published in: Immunologic Research | Issue 3/2008

Abstract

Autoimmunity is a serious health problem and understanding the maintenance and loss of tolerance to self-antigens are key issues in developing new therapeutic strategies to treat these diseases. Despite considerable progress toward understanding B cell tolerance and tolerance loss, much remains unknown, particularly regarding B cells specific for antigens targeted in disease. Our interest in systemic lupus erythematosus (SLE), a B cell-mediated autoimmune disease characterized by the production of autoantibodies to numerous nuclear antigens, is focused on understanding B cell tolerance and tolerance loss to the SLE-specific autoantigen Sm in mice and humans. Our work aims to provide the cellular and molecular underpinnings for the development of rational therapies to target autoreactive B cells in human SLE.

Hahn BH. Antibodies to DNA. N Engl J Med. 1998;338(19):1359–68.PubMedCrossRef

Su W, Madaio MP. Recent advances in the pathogenesis of lupus nephritis: autoantibodies and B cells. Semin Nephrol. 2003;23(6):564–8.PubMedCrossRef

Ciruelo E, de la Cruz J, Lopez I, Gomez-Reino JJ. Cumulative rate of relapse of lupus nephritis after successful treatment with cyclophosphamide. Arthritis Rheum. 1996;39(12):2028–34.PubMedCrossRef

Illei GG, Takada K, Parkin D, Austin HA, Crane M, Yarboro CH, et al. Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: long-term followup of a cohort of 145 patients participating in randomized controlled studies. Arthritis Rheum. 2002;46(4):995–1002.PubMedCrossRef

Nachman PH, Hogan SL, Jennette JC, Falk RJ. Treatment response and relapse in antineutrophil cytoplasmic autoantibody-associated microscopic polyangiitis and glomerulonephritis. J Am Soc Nephrol. 1996;7(1):33–9.PubMed

Harley JB, Alarcon-Riquelme ME, Criswell LA, Jacob CO, Kimberly RP, Moser KL, et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet. 2008;40(2):204–10.PubMedCrossRef

Hom G, Graham RR, Modrek B, Taylor KE, Ortmann W, Garnier S, et al. Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med. 2008;358(9):900–9.PubMedCrossRef

Truedsson L, Bengtsson AA, Sturfelt G. Complement deficiencies and systemic lupus erythematosus. Autoimmunity. 2007;40(8):560–6.PubMedCrossRef

Manderson AP, Botto M, Walport MJ. The role of complement in the development of systemic lupus erythematosus. Annu Rev Immunol. 2004;22:431–56.PubMedCrossRef

10.

Hart SP, Smith JR, Dransfield I. Phagocytosis of opsonized apoptotic cells: roles for ‘old-fashioned’ receptors for antibody and complement. Clin Exp Immunol. 2004;135(2):181–5.PubMedCrossRef

11.

Casciola-Rosen LA, Anhalt G, Rosen A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med. 1994;179(4):1317–30.PubMedCrossRef

12.

Rosen A, Casciola-Rosen L. Autoantigens as substrates for apoptotic proteases: implications for the pathogenesis of systemic autoimmune disease. Cell Death Differ. 1999;6(1):6–12.PubMedCrossRef

13.

Qian Y, Wang H, Clarke SH. Impaired clearance of apoptotic cells induces the activation of autoreactive anti-Sm marginal zone and B-1 B cells. J Immunol. 2004;172(1):625–35.PubMed

14.

Mevorach D, Zhou JL, Song X, Elkon KB. Systemic exposure to irradiated apoptotic cells induces autoantibody production. J Exp Med. 1998;188(2):387–92.PubMedCrossRef

15.

Yong J, Wan L, Dreyfuss G. Why do cells need an assembly machine for RNA-protein complexes? Trends Cell Biol. 2004;14(5):226–32.PubMedCrossRef

16.

Tan EM. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989;44:93–151.PubMedCrossRef

17.

Santulli-Marotto S, Retter MW, Gee R, Mamula MJ, Clarke SH. Autoreactive B cell regulation: peripheral induction of developmental arrest by lupus-associated autoantigens. Immunity. 1998;8(2):209–19.PubMedCrossRef

18.

Bloom DD, Davignon JL, Retter MW, Shlomchik MJ, Pisetsky DS, Cohen PL, et al. V region gene analysis of anti-Sm hybridomas from MRL/Mp-lpr/lpr mice. J Immunol. 1993;150(4):1591–610.PubMed

19.

Borrero M, Clarke SH. Low-affinity anti-Smith antigen B cells are regulated by anergy as opposed to developmental arrest or differentiation to B-1. J Immunol. 2002;168(1):13–21.PubMed

20.

Santulli-Marotto S, Qian Y, Ferguson S, Clarke SH. Anti-Sm B cell differentiation in Ig transgenic MRL/Mp-lpr/lpr mice: altered differentiation and an accelerated response. J Immunol. 2001;166(8):5292–9.PubMed

21.

Qian Y, Conway KL, Lu X, Seitz HM, Matsushima GK, Clarke SH. Autoreactive MZ and B-1 B-cell activation by Faslpr is coincident with an increased frequency of apoptotic lymphocytes and a defect in macrophage clearance. Blood. 2006;108(3):974–82.PubMedCrossRef

22.

Goodnow CC, Cyster JG, Hartley SB, Bell SE, Cooke MP, Healy JI, et al. Self-tolerance checkpoints in B lymphocyte development. Adv Immunol. 1995;59:279–368.PubMedCrossRef

23.

Gay D, Saunders T, Camper S, Weigert M. Receptor editing: an approach by autoreactive B cells to escape tolerance. J Exp Med. 1993;177(4):999–1008.PubMedCrossRef

24.

Nemazee D, Weigert M. Revising B cell receptors. J Exp Med. 2000;191(11):1813–7.PubMedCrossRef

25.

Mandik-Nayak L, Bui A, Noorchashm H, Eaton A, Erikson J. Regulation of anti-double-stranded DNA B cells in nonautoimmune mice: localization to the T-B interface of the splenic follicle. J Exp Med. 1997;186(8):1257–67.PubMedCrossRef

26.

Cyster JG, Hartley SB, Goodnow CC. Competition for follicular niches excludes self-reactive cells from the recirculating B-cell repertoire. Nature. 1994;371(6496):389–95.PubMedCrossRef

27.

Culton DA, O’Conner BP, Conway KL, Diz R, Rutan J, Vilen BJ, et al. Early preplasma cells define a tolerance checkpoint for autoreactive B cells. J Immunol. 2006;176(2):790–802.PubMed

28.

William J, Euler C, Primarolo N, Shlomchik MJ. B cell tolerance checkpoints that restrict pathways of antigen-driven differentiation. J Immunol. 2006;176(4):2142–51.PubMed

29.

Merrell KT, Benschop RJ, Gauld SB, Aviszus K, Decote-Ricardo D, Wysocki LJ, et al. Identification of anergic B cells within a wild-type repertoire. Immunity. 2006;25(6):953–62.PubMedCrossRef

30.

Kilmon MA, Rutan JA, Clarke SH, Vilen BJ. Low-affinity, Smith antigen-specific B cells are tolerized by dendritic cells and macrophages. J Immunol. 2005;175(1):37–41.PubMed

31.

Qian Y, Santiago C, Borrero M, Tedder TF, Clarke SH. Lupus-specific antiribonucleoprotein B cell tolerance in nonautoimmune mice is maintained by differentiation to B-1 and governed by B cell receptor signaling thresholds. J Immunol. 2001;166(4):2412–9.PubMed

32.

Kilmon MA, Wagner NJ, Garland AL, Lin L, Aviszus K, Wysocki LJ, et al. Macrophages prevent the differentiation of autoreactive B cells by secreting CD40 ligand and IL-6. Blood. 2007;110:1595–602.PubMedCrossRef

33.

Lopes-Carvalho T, Kearney JF. Development and selection of marginal zone B cells. Immunol Rev. 2004;197:192–205.PubMedCrossRef

34.

Lopes-Carvalho T, Kearney JF. Marginal zone B cell physiology and disease. Curr Dir Autoimmun. 2005;8:91–123.PubMedCrossRef

35.

Oliver AM, Martin F, Gartland GL, Carter RH, Kearney JF. Marginal zone B cells exhibit unique activation, proliferative and immunoglobulin secretory responses. Eur J Immunol. 1997;27(9):2366–74.PubMedCrossRef

36.

Quartier P, Potter PK, Ehrenstein MR, Walport MJ, Botto M. Predominant role of IgM-dependent activation of the classical pathway in the clearance of dying cells by murine bone marrow-derived macrophages in vitro. Eur J Immunol. 2005;35(1):252–60.PubMedCrossRef

37.

Lesley R, Xu Y, Kalled SL, Hess DM, Schwab SR, Shu HB, Cyster JG. Reduced competitiveness of autoantigen-engaged B cells due to increased dependence on BAFF. Immunity. 2004;20(4):441–53.PubMedCrossRef

38.

Scott RS, McMahon EJ, Pop SM, Reap EA, Caricchio R, Cohen PL, et al. Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature. 2001;411(6834):207–11.PubMedCrossRef

39.

Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992;356(6367):314–7.PubMedCrossRef

40.

Theofilopoulos AN, Dixon FJ. Murine models of systemic lupus erythematosus. Adv Immunol. 1985;37:269–390.PubMedCrossRef

41.

Gerloni M, Lo D, Zanetti M. DNA immunization in relB-deficient mice discloses a role for dendritic cells in IgM→IgG1 switch in vivo. Eur J Immunol. 1998;28(2):516–24.PubMedCrossRef

42.

MacPherson G, Kushnir N, Wykes M. Dendritic cells, B cells and the regulation of antibody synthesis. Immunol Rev. 1999;172:325–34.PubMedCrossRef

43.

Qi H, Egen JG, Huang AY, Germain RN. Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells. Science. 2006;312(5780):1672–6.PubMedCrossRef

44.

Balazs M, Martin F, Zhou T, Kearney J. Blood dendritic cells interact with splenic marginal zone B cells to initiate T-independent immune responses. Immunity. 2002;17(3):341–52.PubMedCrossRef

45.

Baumann I, Kolowos W, Voll RE, Manger B, Gaipl U, Neuhuber WL, et al. Impaired uptake of apoptotic cells into tingible body macrophages in germinal centers of patients with systemic lupus erythematosus. Arthritis Rheum. 2002;46(1):191–201.PubMedCrossRef

46.

Lu Q, Lemke G. Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science. 2001;293(5528):306–11.PubMedCrossRef

47.

Guo Z, Zhang M, An H, Chen W, Liu S, Guo J, et al. Fas ligation induces IL-1beta-dependent maturation and IL-1beta-independent survival of dendritic cells: different roles of ERK and NF-kappaB signaling pathways. Blood. 2003;102(13):4441–7.PubMedCrossRef

48.

Shlomchik MJ, Aucoin AH, Pisetsky DS, Weigert MG. Structure and function of anti-DNA autoantibodies derived from a single autoimmune mouse. Proc Natl Acad Sci USA. 1987;84(24):9150–4.PubMedCrossRef

49.

Shlomchik MJ, Marshak-Rothstein A, Wolfowicz CB, Rothstein TL, Weigert MG. The role of clonal selection and somatic mutation in autoimmunity. Nature. 1987;328(6133):805–11.PubMedCrossRef

50.

Blaese RM, Grayson J, Steinberg AD. Increased immunoglobulin-secreting cells in the blood of patients with active systemic lupus erythematosus. Am J Med. 1980;69(3):345–50.PubMedCrossRef

51.

Budman DR, Merchant EB, Steinberg AD, Doft B, Gershwin ME, Lizzio E, et al. Increased spontaneous activity of antibody-forming cells in the peripheral blood of patients with active SLE. Arthritis Rheum. 1977;20(3):829–33.PubMedCrossRef

52.

Suzuki H, Sakurami T, Imura H. Relationship between reduced B cell susceptibility to IgM antibodies and reduced IgD-bearing B cells in patients with systemic lupus erythematosus. Arthritis Rheum. 1982;25(12):1451–9.PubMedCrossRef

53.

Liossis SN, Kovacs B, Dennis G, Kammer GM, Tsokos GC. B cells from patients with systemic lupus erythematosus display abnormal antigen receptor-mediated early signal transduction events. J Clin Invest. 1996;98(11):2549–57.PubMedCrossRef

54.

Tsokos GC, Wong HK, Enyedy EJ, Nambiar MP. Immune cell signaling in lupus. Curr Opin Rheumatol. 2000;12(5):355–63.PubMedCrossRef

55.

Bijl M, Horst G, Limburg PC, Kallenberg CG. Expression of costimulatory molecules on peripheral blood lymphocytes of patients with systemic lupus erythematosus. Ann Rheum Dis. 2001;60(5):523–6.PubMedCrossRef

56.

Folzenlogen D, Hofer MF, Leung DY, Freed JH, Newell MK. Analysis of CD80 and CD86 expression on peripheral blood B lymphocytes reveals increased expression of CD86 in lupus patients. Clin Immunol Immunopathol. 1997;83(3):199–204.PubMedCrossRef

57.

Odendahl M, Jacobi A, Hansen A, Feist E, Hiepe F, Burmester GR, et al. Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus. J Immunol. 2000;165(10):5970–9.PubMed

58.

Jacobi AM, Odendahl M, Reiter K, Bruns A, Burmester GR, Radbruch A, et al. Correlation between circulating CD27 high plasma cells and disease activity in patients with systemic lupus erythematosus. Arthritis Rheum. 2003;48(5):1332–42.PubMedCrossRef

59.

Smith HR, Olson RR. CD5+ B lymphocytes in systemic lupus erythematosus and rheumatoid arthritis. J Rheumatol. 1990;17(6):833–5.PubMed

60.

Culton DA, Nicholas MW, Bunch DO, Zhen QL, Kepler TB, Dooley MA, et al. Similar CD19 dysregulation in two autoantibody-associated autoimmune diseases suggests a shared mechanism of B-cell tolerance loss. J Clin Immunol. 2007;27(1):53–68.PubMedCrossRef

61.

Falk RJ, Jennette JC. Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N Engl J Med. 1988;318(25):1651–7.PubMed

62.

Jennette JC, Hoidal JR, Falk RJ. Specificity of anti-neutrophil cytoplasmic autoantibodies for proteinase 3. Blood. 1990;75(11):2263–4.PubMed

63.

Jennette JC, Falk RJ. Small-vessel vasculitis. N Engl J Med. 1997;337(21):1512–23.PubMedCrossRef

64.

Nicholas MW, Dooley MA, Hogan SL, Anolik J, Looney J, Sanz I, et al. A novel subset of memory B cells is enriched in autoreactivity and correlates with adverse outcomes in SLE. Clin Immunol. 2008;126(2):189–201.PubMedCrossRef

65.

Narumi S, Takeuchi T, Kobayashi Y, Konishi K. Serum levels of ifn-inducible PROTEIN-10 relating to the activity of systemic lupus erythematosus. Cytokine. 2000;12(10):1561–5.PubMedCrossRef

66.

Okamoto H, Katsumata Y, Nishimura K, Kamatani N. Interferon-inducible protein 10/CXCL10 is increased in the cerebrospinal fluid of patients with central nervous system lupus. Arthritis Rheum. 2004;50(11):3731–2.PubMedCrossRef

Title: Anti-Sm B cell tolerance and tolerance loss in systemic lupus erythematosus
Author: Stephen H. Clarke
Publication date: 01-07-2008
Publisher: Humana Press Inc
Published in: Immunologic Research / Issue 3/2008
Print ISSN: 0257-277X
Electronic ISSN: 1559-0755
DOI: https://doi.org/10.1007/s12026-008-8023-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Anti-Sm B cell tolerance and tolerance loss in systemic lupus erythematosus

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2008

Statins’ immunomodulatory potential against Th17 cell-mediated autoimmune response

TCR-MHC docking orientation: natural selection, or thymic selection?

Microglial cells and Parkinson’s disease

Parameters influencing antigen-specific immunotherapy for type 1 diabetes

NF-κB pathways in the immune system: control of the germinal center reaction

The evolving role of semaphorins and plexins in the immune system: Plexin-A1 regulation of dendritic cell function