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Research Article

Autoantibody-dependent and autoantibody-independent roles for B cells in systemic lupus erythematosus: Past, present, and future

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Pages 84-97 | Published online: 17 Dec 2009

References

  • Tan EM. Antinuclear antibodies: Diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989; 44:93–151.
  • Reichlin M. Ribosomal P antibodies and CNS lupus. Lupus. 2003; 12:916–918.
  • Ruiz-Irastorza G, Khamashta MA, Hughes GR. Hughes syndrome crosses boundaries. Autoimmun Rev. 2002; 1:43–48.
  • Buyon JP, Clancy RM. Neonatal lupus: Review of proposed pathogenesis and clinical data from the US-based Research Registry for Neonatal Lupus. Autoimmunity. 2003; 36:41–50.
  • Ceppellini R, Polli E, Celada F. A DNA-reaction factor in serum of a patient with lupus erythematosus diffusus. Proc Soc Exp Biol Med. 1957; 96:572–574.
  • Robbins WD, Holman HR, Deicher H, Kunkel HG. Complement fixation with cell nuclei and DNA in lupus erythematosus. Proc Soc Exp Biol Med. 1957; 96:575–579.
  • Massardo L, Martinez ME, Jacobelli S, Villarroel L, Rosenberg H, Rivero S. Survival of Chilean patients with systemic lupus erythematosus. Semin Arthritis Rheum. 1994; 24:1–11.
  • Mikdashi J, Handwerger B. Predictors of neuropsychiatric damage in systemic lupus erythematosus: Data from the Maryland lupus cohort. Rheumatology. 2004; 42:1555–1560.
  • Toloza SM, Roseman JM, Alarcon GS, McGwin GJr., Uribe AG, Fessler BJ, Bastian HM, Vilá LM, Wu R, Shoenfeld Y, Roseman JM, Reveille JD. LUMINA Study Group. Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXII. Predictors of time to the occurrence of initial damage. Arthritis Rheum. 2004; 50:3177–3186.
  • Yee CS, Hussein H, Skan J, Bowman S, Situnayake D, Gordon C. Association of damage with autoantibody profile, age, race, sex and disease duration in systemic lupus erythematosus. Rheumatology. 2003; 42:276–279.
  • Morimoto C, Sano H, Abe T, Homma M, Steinberg AD. Correlation between clinical activity of systemic lupus erythematosus and the amounts of DNA in DNA/anti-DNA antibody immune complexes. J Immunol. 1982; 139:1960–1965.
  • Ter Borg EJ, Horst G, Hummel EJ, Limburg PC, Kallenberg CG. Measurement of increases in double-stranded DNA antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus: A cross-sectional study. Rheumatology. 2001; 40:1405–1412.
  • Bastian HM, Roseman JM, McGwin GJr., Alarcón GS, Friedman AW, Fessler BJ, Baethge BA, Reveille JD, LUMINA Study Group. Lupus in minority populations: Nature vs nurture. Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis. Lupus. 2002; 11:152–160.
  • Alba P, Bento L, Cuadrado MJ, Karim Y, Tungekar MF, Abbs I, Khamashta MA, D'Cruz D, Hughes GR. Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: Significant factors associated with lupus nephritis. Ann Rheum Dis. 2003; 62:556–560.
  • Cortés-Hernández J, Ordi-Ros J, Labrador M, Buján S, Balada E, Segarra A, Vilardell-Tarrés M. Antihistone and anti-double-stranded deoxyribonucleic acid antibodies are associated with renal disease in systemic lupus erythematosus. Am J Med. 2004; 116:165–173.
  • Forger F, Matthias T, Oppermann M, Becker H, Helmke K. Clinical significance of anti-dsDNA antibody isotypes: IgG/IgM ratio of anti-dsDNA antibodies as a prognostic marker for lupus nephritis. Lupus. 2004; 12:36–44.
  • Manger K, Manger B, Repp R, Geisselbrecht M, Geiger A, Pfahlberg A, Harrer T, Kalden JR. Definition of risk factors for death, end stage renal disease and thromboembolic events in a monocentric cohort of 338 patients with systemic lupus erythematosus. Ann Rheum Dis. 2002; 61:1065–1070.
  • MacGowan JR, Ellis S, Griffiths M, Isenberg DA. Retrospective analysis of outcome in a cohort of patients with lupus nephritis treated between 1977 and 1999. Rheumatology. 2002; 41:981–987.
  • Adler MK, Baumgarten A, Hecht B, Siegel NJ. Prognostic significance of DNA-binding capacity patterns in patients with lupus nephritis. Ann Rheum Dis. 1975; 34:444–450.
  • Ravirajan CT, Rowse L, MacGowan JR, Isenberg DA. An analysis of clinical disease activity and nephritis-associated serum autoantibody profiles in patients with systemic lupus erythematosus: A cross-sectional study. Rheumatology. 2001; 40:1405–1412.
  • Helyer BJ, Howie JB. Renal disease associated with positive lupus erythematosus tests in a cross-bred strain of mice. Nature. 1963; 197:197.
  • Andrews BS, Eisenberg RA, Theofilopoulos AN, Izui S, Wilson CB, McConahey PJ, Murphy ED, Roths JB, Dixon FJ. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978; 148:1198–1215.
  • Melez KA, Reeves JP, Steinberg AD. Regulation of the expression of autoimmunity in NZB × NZW F1 mice by sex hormones. J Immunopharmacol. 1978–1979; 1:27–42.
  • Lambert PH, Dixon FJ. Pathogenesis of the glomerulonephritis of NZB/W mice. J Exp Med. 1968; 127:507–522.
  • Hurd ER, Ziff M. Quantitative studies of immunoglobulin deposition in the kidney, glomerular cell proliferation and glomerulosclerosis in NZB/NZW F1 hybrid mice. Clin Exp Immunol. 1977; 27:261–268.
  • 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; 356:314–317.
  • Sakata K, Sakata A, Kong L, Dang H, Talal N. Role of Fas/FasL interaction in physiology and pathology: The good and the bad. Clin Immunol Immunopathol. 1998; 87:1–7.
  • Theofilopoulos AN, Dixon FJ. Murine models of systemic lupus erythematosus. Adv Immunol. 1985; 37:269–390.
  • Koffler D, Schur PH, Kunkel HG. Immunological studies concerning the nephritis of systemic lupus erythematosus. J Exp Med. 1967; 126:607–624.
  • Vlahakos DV, Foster MH, Adams S, Katz M, Ucci AA, Barrett KJ, Datta SK, Madaio MP. Anti-DNA antibodies form immune deposits at distinct glomerular and vascular sites. Kidney Int. 1992; 41:1690–1700.
  • Jonsson R, Svalander C, Nyberg G. Immune deposits in oral mucosa, skin and kidney in patients with systemic lupus erythematosus. Clin Exp Rheumatol. 1986; 4:231–236.
  • Dang H, Harbeck RJ. The in vivo and in vitro glomerular deposition of isolated anti-double-stranded-DNA antibodies in NZB/W mice. Clin Immunol Immunopathol. 1984; 30:265–278.
  • Raz E, Brezis M, Rosenmann E, Eilat D. Anti-DNA antibodies bind directly to renal antigens and induce kidney dysfunction in the isolated perfused rat kidney. J Immunol. 1989; 142:3076–3082.
  • D'Andrea DM, Coupaye-Gerard B, Kleyman TR, Foster MH, Madaio MP. Lupus autoantibodies interact directly with distinct glomerular and vascular cell surface antigens. Kidney Int. 1996; 49:1214–1221.
  • Vargas MT, Gustilo K, D'Andrea DM, Kalluri R, Foster MH, Madaio MP. Structural features of nephritogenic lupus autoantibodies. Methods. 1997; 11:62–69.
  • Ehrenstein MR, Katz DR, Griffiths MH, Papadaki L, Winkler TH, Kalden JR, Isenberg DA. Human IgG anti-DNA antibodies deposit in kidneys and induce proteinuria in SCID mice. Kidney Int. 1995; 48:705–711.
  • LeBlanc BA, Urowitz MB, Gladman OD. Serologically active, clinically quiescent systemic lupus erythematosus—longterm follow-up. J Rheumatol. 1994; 21:174–175.
  • Gladman DD, Hirani N, Ibañez D, Urowitz MB. Clinically active serologically quiescent systemic lupus erythematosus. J Rheumatol. 2003; 30:1960–1962.
  • Lewis EJ, Hunsicker LG, Lan SP, Rohde RD, Lachin JM. A controlled trial of plasmapheresis therapy in severe lupus nephritis. The Lupus Nephritis Collaborative Study Group. N Engl J Med. 1992; 326:1373–1379.
  • Looney RJ, Anolik JH, Campbell D, Felgar RE, Young F, Arend LJ, Sloand JA, Rosenblatt J, Sanz I. B cell depletion as a novel treatment for systemic lupus erythematosus: A phase I/II dose-escalation trial of rituximab. Arthritis Rheum. 2004; 50:2580–2589.
  • Wellmann U, Letz M, Schneider A, Amann K, Winkler TH. An Ig mu-heavy chain transgene inhibits systemic lupus erythematosus immunopathology in autoimmune (NZB × NZW)F1 mice. Int Immunol. 2001; 13:1461–1469.
  • Kong PL, Zhu T, Madaio MP, Craft J. Role of the H-2 haplotype in Fas-intact lupus-prone MRL mice: Association with autoantibodies but not renal disease. Arthritis Rheum. 2003; 48:2992–2995.
  • Rudofsky UH, Evans BD, Balaban SL, Mottironi VD, Gabrielsen AE. Differences in expression of lupus nephritis in New Zealand mixed H-2z homozygous inbred strains of mice derived from New Zealand black and New Zealand white mice. Origins and initial characterization. Lab Invest. 1993; 68:419–426.
  • Jacob CO, Zang S, Li L, Ciobanu V, Quismorio F, Mizutani A, Satoh M, Koss M. Pivotal role of Stat4 and Stat6 in the pathogenesis of the lupus-like disease in the New Zealand mixed 2328 mice. J Immunol. 2003; 171:1564–1571.
  • Jacob CO, Pricop L, Putterman C, Koss MN, Liu Y, Kollaros M, Bixler SA, Ambrose CM, Scott ML, Stohl W. Paucity of clinical disease despite serological autoimmunity and kidney pathology in lupus-prone New Zealand mixed 2328 mice deficient in BAFF. J Immunol. 2006; 177:2671–2680.
  • Ohnishi K, Ebling FM, Mitchell B, Singh RR, Hahn BH, Tsao BP. Comparison of pathogenic and non-pathogenic murine antibodies to DNA: Antigen binding and structural characteristics. Int Immunol. 1994; 6:817–830.
  • Takahashi S, Nose M, Sasaki J, Yamamoto T, Kyogoku M. IgG3 production in MRL/lpr mice is responsible for development of lupus nephritis. J Immunol. 1991; 147:515–519.
  • Amoura Z, Koutouzov S, Chabre H, Cacoub P, Amoura I, Musset L, Bach JF, Piette JC. Presence of antinucleosome autoantibodies in a restricted set of connective tissue diseases: Antinucleosome antibodies of the IgG3 subclass are markers of renal pathogenicity in systemic lupus erythematosus. Arthritis Rheum. 2000; 43:76–84.
  • Shlomchik MJ, Madaio MP, Ni D, Trounstein M, Huszar D. The role of B cells in lpr/lpr-induced autoimmunity. J Exp Med. 1994; 180:1295–1306.
  • Chan OT, Madaio MP, Shlomchik MJ. B cells are required for lupus nephritis in the polygenic, Fas-intact MRL model of systemic autoimmunity. J Immunol. 1999; 163:3592–3596.
  • Singh RR, Saxena V, Zang S, Li L, Finkelman FD, Witte DP, Jacob CO. Differential contribution of IL-4 and STAT6 vs STAT4 to the development of lupus nephritis. J Immunol. 2003; 170:4818–4825.
  • Chan OT, Hannum LG, Haberman AM, Madaio MP, Shlomchik MJ. A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus. J Exp Med. 1999; 189:1639–1648.
  • Chesnut RW, Grey HM. Studies on the capacity of B cells to serve as antigen-presenting cells. J Immunol. 1981; 126:1075–1079.
  • Ron Y, Sprent J. T cell priming in vivo: A major role for B cells in presenting antigen to T cells in lymph nodes. J Immunol. 1987; 138:2848–2856.
  • Kurt-Jones EA, Liano D, HayGlass KA, Benacerraf B, Sy MS, Abbas AK. The role of antigen-presenting B cells in T cell priming in vivo. Studies of B cell-deficient mice. J Immunol. 1988; 140:3773–3778.
  • Constant S, Schweitzer N, West J, Ranney P, Bottomly K. B lymphocytes can be competent antigen-presenting cells for priming CD4+T cells to protein antigens in vivo. J Immunol. 1995; 155:3734–3741.
  • Crawford A, Macleod M, Schumacher T, Corlett L, Gray D. Primary T cell expansion and differentiation in vivo requires antigen presentation by B cells. J Immunol. 2006; 176:3498–3506.
  • Mamula MJ, Lin RH, Janeway CAJr., Hardin JA. Breaking T cell tolerance with foreign and self co-immunogens. A study of autoimmune B and T cell epitopes of cytochrome c. J Immunol. 1992; 149:789–795.
  • Lin RH, Mamula MJ, Hardin JA, Janeway CAJr.. Induction of autoreactive B cells allows priming of autoreactive T cells. J Exp Med. 1991; 173:1433–1439.
  • Mamula MJ, Fatenejad S, Craft J. B cells process and present lupus autoantigens that initiate autoimmune T cell responses. J Immunol. 1994; 152:1453–1461.
  • Shan H, Shlomchik MJ, Marshak-Rothstein A, Pisetsky DS, Litwin S, Weigert MG. The mechanism of autoantibody production in an autoimmune MRL/lpr mouse. J Immunol. 1994; 153:5104–5120.
  • Shlomchik MJ, Marshak-Rothstein A, Wolfowicz CB, Rothstein TL, Weigert MG. The role of clonal selection and somatic mutation in autoimmunity. Nature. 1987; 328:805–811.
  • Randen I, Brown D, Thompson KM, Hughes-Jones N, Pascual V, Victor K, Capra JD, Førre O, Natvig JB. Clonally related IgM rheumatoid factors undergo affinity maturation in the rheumatoid synovial tissue. J Immunol. 1992; 148:3296–3301.
  • Chan O, Shlomchik MJ. A new role for B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice. J Immunol. 1998; 160:51–59.
  • Jacob N, Yang H, Pricop L, Liu Y, Gao X, Zheng SG, Wang J, Gao HX, Putterman C, Koss MN, Stohl W, Jacob CO. Accelerated pathological and clinical nephritis in systemic lupus erythematosus-prone New Zealand Mixed 2328 mice doubly deficient in TNF receptor 1 and TNF receptor 2 via a Th17-associated pathway. J Immunol. 2009; 182:2532–2541.
  • Greenfield EA, Nguyen KA, Kuchroo VK. CD28/B7 costimulation: A review. Crit Rev Immunol. 1998; 18:389–418.
  • Kremer JM, Westhovens R, Leon M, Di Giorgio E, Alten R, Steinfeld S, Russell A, Dougados M, Emery P, Nuamah IF, Williams GR, Becker JC, Hagerty DT, Moreland LW. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med. 2003; 349:1907–1915.
  • Finck BK, Linsley PS, Wofsy D. Treatment of murine lupus with CTLA4Ig. Science. 1994; 265:1225–1227.
  • Davidson A, Diamond B, Wofsy D, Daikh D. Block and tackle: CTLA4Ig takes on lupus. Lupus. 2005; 14:197–203.
  • Rodríguez-Pinto D, Moreno J. B cells can prime naive CD4+T cells in vivo in the absence of other professional antigen-presenting cells in a CD154–CD40-dependent manner. Eur J Immunol. 2005; 35:1097–1105.
  • Grewal IS, Xu J, Flavell RA. Impairment of antigen-specific T-cell priming in mice lacking CD40 ligand. Nature. 1995; 378:617–620.
  • Stüber E, Strober W, Neurath M. Blocking the CD40L–CD40 interaction in vivo specifically prevents the priming of T helper 1 cells through the inhibition of interleukin-12 secretion. J Exp Med. 1996; 183:693–698.
  • van Essen D, Kikutani H, Gray D. CD40 ligand-transduced co-stimulation of T cells in the development of helper function. Nature. 1995; 378:620–623.
  • Blotta MH, Marshall JD, DeKruyff RH, Umetsu DT. Cross-linking of the CD40 ligand on human CD4+ T lymphocytes generates a costimulatory signal that up-regulates IL-4 synthesis. J Immunol. 1996; 156:3133–3140.
  • Foy TM, Aruffo A, Bajorath J, Buhlman JE, Neolle RJ. Immune regulation by CD40 and its ligand gp39. Annu Rev Immunol. 1996; 14:591–617.
  • Kawabe T, Naka T, Yoshida K, Tanaka T, Fujiwara H, Suematsu S, Yoshida N, Kishimoto T, Kikutani H. The immune responses in CD40-deficient mice: Impaired immunoglobulin class switching and germinal center formation. Immunity. 1994; 1:167–178.
  • Renshaw BR, Fanslow WC, Armitage RJ, Cambell KA, Liggit D, Wright B, Davison BL, Maliszewski CR. Humoral immune responses in CD40 ligand-deficient mice. J Exp Med. 1994; 180:1889–1900.
  • Duddy ME, Alter A, Bar-Or A. Distinct profiles of human B cell effector cytokines: A role in immune regulation?. J Immunol. 2004; 172:3422–3427.
  • Ma J, Xu J, Madaio MP, Peng Q, Zhang J, Grewal IS, Flavell RA, Craft J. Autoimmune lpr/lpr mice deficient in CD40 ligand spontaneous Ig class switching with dichotomy of autoantibody responses. J Immunol. 1996; 157:417–426.
  • Wang X, Huang W, Schiffer LE, Mihara M, Akkerman A, Hiromatsu K, Davidson A. Effects of anti-CD154 treatment on B cells in murine systemic lupus erythematosus. Arthritis Rheum. 2003; 48:495–506.
  • Moser KL, Neas BR, Salmon JE, Yu H, Gray-McGuire C, Asundi N, Bruner GR, Fox J, Kelly J, Henshall S, Bacino D, Dietz M, Hogue R, Koelsch G, Nightingale L, Shaver T, Abdou NI, Albert DA, Carson C, Petri M, Treadwell EL, James JA, Harley JB. Genome scan of human systemic lupus erythematosus: Evidence for linkage on chromosome 1q in African-American pedigrees. Proc Natl Acad Sci USA. 1998; 95:14869 − 14874.
  • Shai R, Quismorio FPJr., Li L, Kwon OJ, Morrison J, Wallace DJ, Neuwelt CM, Brautbar C, Gauderman WJ, Jacob CO. Genome-wide screen for systemic lupus erythematosus susceptibility genes in multiplex families. Hum Mol Genet. 1999; 8:639–644.
  • Gaffney PM, Ortmann WA, Selby SA, Shark KB, Ockenden TC, Rohlf KE, Walgrave NL, Boyum WP, Malmgren ML, Miller ME, Kearns GM, Messner RP, King RA, Rich SS, Behrens TW. Genome screening in human systemic lupus erythematosus: Results from a second Minnesota cohort and combined analyses of 187 sib-pair families. Am J Hum Genet. 2000; 66:547–556.
  • Chadha S, Miller K, Farwell L, Lightstone LB, Daly MJ, Rioux JD, Vyse TJ. Haplotype structure of TNFRSF5–TNFSF5 (CD40–CD40L) and association analysis in systemic lupus erythematosus. Eur J Hum Genet. 2005; 13:669–676.
  • Gaffney PM, Langefeld CD, Graham RR, Ortmann WA, Williams AH, Rodine PR, Moser KL, Behrens TW. Fine-mapping chromosome 20 in 230 systemic lupus erythematosus sib pair and multiplex families: Evidence for genetic epistasis with chromosome16q12. Am J Hum Genet. 2006; 78:747–758.
  • Koshy M, Berger D, Crow MK. Increased expression of CD40 ligand on systemic lupus erythematosus lymphocytes. J Clin Invest. 1996; 98:826–837.
  • Desai-Mehta A, Lu L, Ramsey-Goldman R, Datta SK. Hyperexpression of CD40 ligand by B and T cells in human lupus and its role in pathogenic autoantibody production. J Clin Invest. 1996; 97:2063–2073.
  • Kato K, Santana-Sahagun E, Rassenti L, Weisman MH, Tumura N, Kobayashi S, Hashimoto H, Kipps TJ. The soluble CD40 ligand sCD154 in systemic lupus erythematosus. J Clin Invest. 1999; 104:947–955.
  • Huang W, Sinha J, Newman J, Reddy B, Budhai L, Furie R, Vaishnaw A, Davidson A. The effect of anti-CD40 ligand antibody on B cells in human systemic lupus erythematosus. Arthritis Rheum. 2002; 46:1554–1562.
  • Kalunian KC, Davis JCJr., Merrill JT, Totoritis MC, Wofsy D, IDEC-131 Lupus Study Group. Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154: A randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002; 46:3251–3258.
  • Boumpas DT, Furie R, Manzi S, Illei GG, Wallace DJ, Balow JE, Vaishnaw A, BG9588 Lupus Nephritis Trial Group.. A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis. Arthritis Rheum. 2003; 48:719–727.
  • Sfikakis PP, Boletis JN, Lionaki S, Vigklis V, Fragiadaki KG, Iniotaki A, Moutsopoulos HM. Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand: An open-label trial. Arthritis Rheum. 2005; 52:501–513.
  • Pistoia V. Production of cytokines by human B cells in health and disease. Immunol Today. 1997; 18:343–350.
  • Elliott MJ, Maini RN, Feldmann M, Kalden JR, Antoni C, Smolen JS, Leeb B, Breedveld FC, Macfarlane JD, Bijl HA. Randomized double-blind comparison of chimeric monoclonal antibody to tumor necrosis factorα(cA2) versus placebo in rheumatoid arthritis. Lancet. 1994; 344:1105–1110.
  • Van Dulleman HM, van Deventer SJ, Hommes DW, Bijl HA, Jansen J, Tytgat GN, Woody J. Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroentrology. 1995; 109:129–135.
  • Aringer M, Steiner G, Graninger WB, Höfler E, Steiner CW, Smolen JS. Effects of short-term infliximab therapy on autoantibodies in systemic lupus erythematosus. Arthritis Rheum. 2007; 56:274–279.
  • Koutouzov S, Mathian A, Dalloul A. Type-I interferons and systemic lupus erythematosus. Autoimmun Rev. 2006; 5:554–562.
  • Pascual V, Farkas L, Banchereau J. Systemic lupus erythematosus: All roads lead to type I interferons. Curr Opin Immunol. 2006; 18:676–682.
  • Agrawal H, Jacob N, Carreras E, Bajana S, Putterman C, Turner S, Neas B, Mathian A, Koss MN, Stohl W, Kovats S, Jacob CO. Deficiency of type I IFN receptor in lupus prone NZM 2328 mice decreases dendritic cell numbers and activation and protects from disease. J Immunol. 2009; 183:6021–6029.
  • Rönnblom L, Pascual V. The innate immune system in SLE: Type I interferons and dendritic cells. Lupus. 2008; 17:394–399.
  • Kishimoto T. Interleukin-6: From basic science to medicine—40 years in immunology. Annu Rev Immunol. 2005; 23:1–21.
  • Liang B, Gardner DB, Griswold DE, Bugelski PJ, Song XY. Anti-interleukin-6 monoclonal antibody inhibits autoimmune responses in a murine model of systemic lupus erythematosus. Immunology. 2006; 119:296–305.
  • Aran AA, Putterman C. Treatment of lupus nephritis: Facing the era of immunotherapy. Panminerva Med. 2008; 50:235–245.
  • Steinmetz OM, Velden J, Kneissler U, Marx M, Klein A, Helmchen U, Stahl RA, Panzer U. Analysis and classification of B-cell infiltrates in lupus and ANCA-associated nephritis. Kidney Int. 2008; 74:448–457.
  • Harris DP, Haynes L, Sayles PC, Duso DK, Eaton SM, Lepak NM, Johnson LL, Swain SL, Lund FE. Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol. 2000; 1:475–482.
  • Tumanov A, Kuprash D, Lagarkova M, Grivennikov S, Abe K, Shakhov A, Drutskaya L, Stewart C, Chervonsky A, Nedospasov S. Distinct role of surface lymphotoxin expressed by B cells in the organization of secondary lymphoid tissues. Immunity. 2002; 17:239–250.
  • Gonzalez M, Mackay F, Browning JL, Kosco-Vilbois MH, Noelle RJ. The sequential role of lymphotoxin and B cells in the development of splenic follicles. J Exp Med. 1998; 187:997–1007.
  • Moulin V, Andris F, Thielemans K, Maliszewski C, Urbain J, Moser M. B lymphocytes regulate dendritic cell (DC) function in vivo: Increased interleukin 12 production by DCs from B cell-deficient mice results in T helper cell type 1 deviation. J Exp Med. 2000; 192:475–482.
  • Golovkina TV, Shlomchik M, Hannum L, Chervonsky A. Organogenic role of B lymphocytes in mucosal immunity. Science. 1999; 286:1965–1968.
  • Crowley MT, Reilly CR, Lo D. Influence of lymphocytes on the presence and organization of dendritic cell subsets in the spleen. J Immunol. 1999; 163:4894–4900.
  • Luther SA, Lopez T, Bai W, Hanahan D, Cyster JG. BLC expression in pancreatic islets causes B cell recruitment and lymphotoxin-dependent lymphoid neogenesis. Immunity. 2000; 12:47181.
  • De Togni P, Goellner J, Ruddle NH, Streeter PR, Fick A, Mariathasan S, Smith SC, Carlson R, Shornick LP, Strauss-Schoenberger J. Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science. 1994; 264:703–707.
  • Wang Y, Wang J, Sun Y, Wu Q, Fu YX. Complementary effects of TNF and lymphotoxin on the formation of germinal center and follicular dendritic cells. J Immunol. 2001; 166:330–337.
  • Ware CF. Network communications: Lymphotoxins, LIGHT, and TNF. Annu Rev Immunol. 2005; 23:787–819.
  • Anolik JH. B cell biology and dysfunction in SLE. Bull NYU Hosp Jt Dis. 2007; 65:182–186.
  • Moore KW, de Waal Malefyt R, Coffman RL, O'Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001; 19:683–765.
  • Mauri C, Ehrenstein MR. The ‘short’ history of regulatory B cells. Trends Immunol. 2008; 29:34–40.
  • Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK. Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity. 2002; 16:219–230.
  • Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM. B cells regulate autoimmunity by provision of IL-10. Nat Immunol. 2002; 3:944–950.
  • Blair PA, Chavez-Rueda KA, Evans JG, Shlomchik MJ, Eddaoudi A, Isenberg DA, Ehrenstein MR, Mauri C. Selective targeting of B cells with agonistic anti-CD40 is an efficacious strategy for the generation of induced regulatory T2-like B cells and for the suppression of lupus in MRL/lpr mice. J Immunol. 2009; 182:3492–3502.
  • Stohl W, Looney RJ. B cell depletion therapy in systemic rheumatic diseases: Different strokes for different folks?. Clin Immunol. 2006; 121:1–12.
  • Nwobi O, Abitbol CL, Chandar J, Seeherunvong W, Zilleruelo G. Rituximab therapy for juvenile-onset systemic lupus erythematosus. Pediatr Nephrol. 2008; 23:413–419.
  • Camous L, Melander C, Vallet M, Squalli T, Knebelmann B, Noël LH, Fakhouri F. Complete remission of lupus nephritis with rituximab and steroids for induction and rituximab alone for maintenance therapy. Am J Kidney Dis. 2008; 52:346–352.
  • Leandro MJ, Cambridge G, Edwards JC, Ehrenstein MR, Isenberg DA. B-cell depletion in the treatment of patients with systemic lupus erythematosus: A longitudinal analysis of 24 patients. Rheumatology (Oxford). 2005; 44:1542–1545.
  • van Vollenhoven RF, Gunnarsson I, Welin-Henriksson E, Sundelin B, Osterborg A, Jacobson SH, Klareskog L. Biopsy-verified response of severe lupus nephritis to treatment with rituximab (anti-CD20 monoclonal antibody) plus cyclophosphamide after biopsy-documented failure to respond to cyclophosphamide alone. Scand J Rheumatol. 2004; 33:423–427.
  • Gunnarsson I, Sundelin B, Jónsdóttir T, Jacobson SH, Henriksson EW, van Vollenhoven RF. Histopathologic and clinical outcome of rituximab treatment in patients with cyclophosphamide-resistant proliferative lupus nephritis. Arthritis Rheum. 2007; 56:1263–1272.
  • Jónsdóttir T, Gunnarsson I, Risselada A, Henriksson EW, Klareskog L, van Vollenhoven RF. Treatment of refractory SLE with rituximab plus cyclophosphamide: Clinical effects, serological changes, and predictors of response. Ann Rheum Dis. 2008; 67:330–334.
  • Merrill JT, Neuwelt CM, Wallace DJ, Shanahan JC, Latinis KM, Oates JC, Utset TO, Gordon C, Isenberg DA, Hsieh HJ, Zhang D, Brunetta PG. Efficacy and safety of rituximab in patients with moderately to severely active systemic lupus erythematosus: Results from the randomized, double-blind phase II/III study EXPLORER. Arthritis Rheum. 2008; 58:4029–4030.
  • Furie R, Looney RJ, Rovin B, Latinis KM, Appel G, Sanchez-Guerrero J, Fervenza FC, Maciuca R, Brunetta P, Zhang D, Garg J. Efficacy and safety of rituximab in subjects with active proliferative lupus nephritis (LN): results from the randomized, double-blind phase III LUNAR study. Arthritis Rheum. 2009; 60:S429.
  • Fujimoto M, Poe JC, Hasegawa M, Tedder TF. CD19 regulates intrinsic B lymphocyte signal transduction and activation through a novel mechanism of processive amplification. Immunol Res. 2000; 22:281–298.
  • Harada Y, Kawano MM, Huang N, Mahmoud MS, Lisukov IA, Mihara K, Tsujimoto T, Kuramoto A. Identification of early plasma cells in peripheral blood and their clinical significance. Br J Haematol. 1996; 92:184–191.
  • Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K, Xu W, Parrish-Novak J, Foster D, Lofton-Day C, Moore M, Littau A, Grossman A, Haugen H, Foley K, Blumberg H, Harrison K, Kindsvogel W, Clegg CH. TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature. 2000; 404:995–999.
  • Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P, Tschopp J, Browning JL. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999; 190:1697–1710.
  • Khare SD, Sarosi I, Xia XZ, McCabe S, Miner K, Solovyev I, Hawkins N, Kelley M, Chang D, Van G, Ross L, Delaney J, Wang L, Lacey D, Boyle WJ, Hsu H. Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice. Proc Natl Acad Sci USA. 2000; 97:3370–3375.
  • Stohl W, Xu D, Kim KS, Koss MN, Jorgensen TN, Deocharan B, Metzger TE, Bixler SA, Hong YS, Ambrose CM, Mackay F, Morel L, Putterman C, Kotzin BL, Kalled SL. BAFF overexpression and accelerated glomerular disease in mice with an incomplete genetic predisposition to systemic lupus erythematosus. Arthritis Rheum. 2005; 52:2080–2091.
  • Kayagaki N, Yan M, Seshasayee D, Wang H, Lee W, French DM, Grewal IS, Cochran AG, Gordon NC, Yin J, Starovasnik MA, Dixit VM. BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-κB2. Immunity. 2002; 17:515–524.
  • Ramanujam M, Wang X, Huang W, Liu Z, Schiffer L, Tao H, Frank D, Rice J, Diamond B, Yu KO, Porcelli S, Davidson A. Similarities and differences between selective and nonselective BAFF blockade in murine SLE. J Clin Invest. 2006; 116:724–734.
  • Ramanujam M, Wang X, Huang W, Schiffer L, Grimaldi C, Akkerman A, Diamond B, Madaio MP, Davidson A. Mechanism of action of transmembrane activator and calcium modulator ligand interactor-Ig in murine systemic lupus erythematosus. J Immunol. 2004; 173:3524–3534.
  • Zhang J, Roschke V, Baker KP, Wang Z, Alarcón GS, Fessler BJ, Bastian H, Kimberly RP, Zhou T. Cutting edge: A role for B lymphocyte stimulator in systemic lupus erythematosus. J Immunol. 2001; 166:6–10.
  • Cheema GS, Roschke V, Hilbert DM, Stohl W. Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum. 2001; 44:1313–1319.
  • 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; 20:441–453.
  • Thien M, Phan TG, Gardam S, Amesbury M, Basten A, Mackay F, Brink R. Excess BAFF rescues self-reactive B cells from peripheral deletion and allows them to enter forbidden follicular and marginal zone niches. Immunity. 2004; 20:785–798.
  • Jacobi AM, Odendahl M, Reiter K, Bruns A, Burmester GR, Radbruch A, Valet G, Lipsky PE, Dõrner T. Correlation between circulating CD27high plasma cells and disease activity in patients with systemic lupus erythematosus. Arthritis Rheum. 2003; 48:1332–1342.
  • Avery DT, Kalled SL, Ellyard JI, Ambrose C, Bixler SA, Thien M, Brink R, Mackay F, Hodgkin PD, Tangye SG. BAFF selectively enhances the survival of plasmablasts generated from human memory B cells. J Clin Invest. 2003; 112:286–297.
  • Baker KP, Edwards BM, Main SH, Choi GH, Wager RE, Halpern WG, Lappin PB, Riccobene T, Abramian D, Sekut L, Sturm B, Poortman C, Minter RR, Dobson CL, Williams E, Carmen S, Smith R, Roschke V, Hilbert DM, Vaughan TJ, Albert VR. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum. 2003; 48:3253–3265.
  • Wallace DJ, Stohl W, Furie RA, Lisse JR, McKay JD, Merrill JT, Petri MA, Ginzler EM, Chatham WW, McCune WJ, Fernandez V, Chevrier MR, Zhong J, Freimuth WW. A phase II, randomized, double-blind, placebo-controlled, dose-ranging study of belimumab in patients with active systemic lupus erythematosus. Arthritis Rheum. 2009; 61:1168–1178.
  • Furie RA, Petri MA, Wallace DJ, Ginzler EM, Merrill JT, Stohl W, Chatham WW, Strand V, Weinstein A, Chevrier MR, Zhong ZJ, Freimuth WW. Novel evidence-based systemic lupus erythematosus responder index. Arthritis Rheum. 2009; 61:1143–1151.
  • Navarra S, Guzman R, Gallacher A, Levy RA, Li EK, Thomas M, Jimenez R, Leon M, Hall S, Lan JL, Nasonov E, Tanasescu C, Kim HY, Pineda L, Zhong ZJ, Freimuth W. Belimumab, a BLyS-specific inhibitor, reduced disease activity, flares and prednisone use in patients with active SLE: efficacy and safety results from the phase 3 BLISS-52 study. Arthritis Rheum. 2009; 60:3859.
  • Coutts SM, Plunkett ML, Iverson GM, Barstad PA, Berner CM. Pharmacological intervention in antibody mediated disease. Lupus. 1996; 5:158–159.
  • Furie RA, Cash JM, Cronin ME, Katz RS, Weisman MH, Aranow C, Liebling MR, Hudson NP, Berner CM, Coutts S, de Haan HA. Treatment of systemic lupus erythematosus with LJP 394. J Rheumatol. 2001; 28:257–265.
  • Alarcón-Segovia D, Tumlin JA, Furie RA, McKay JD, Cardiel MH, Strand V, Bagin RG, Linnik MD, Hepburn B, LJP 394 Investigator Consortium.. LJP 394 for the prevention of renal flare in patients with systemic lupus erythematosus: Results from a randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2003; 48:442–454.
  • Cardiel MH, Tumlin JA, Furie RA, Wallace DJ, Joh T, Linnik MD, LJP 394-90-09 Investigator Consortium. Abetimus sodium for renal flare in systemic lupus erythematosus: Results of a randomized, controlled phase III trial. Arthritis Rheum. 2008; 58:2470–2480.
  • Sato S, Tuscano JM, Inaoki M, Tedder TF. CD22 negatively and positively regulates signal transduction through the B lymphocyte antigen receptor. Semin Immunol. 1998; 10:287–297.
  • Walker JA, Smith KG. CD22: An inhibitory enigma. Immunology. 2008; 123:314–325.
  • Dörner T, Goldenberg DM. Targeting CD22 as a strategy for treating systemic autoimmune diseases. Ther Clin Risk Manag. 2007; 3:953–959.
  • Bolland S, Ravetch JV. Spontaneous autoimmune disease in Fc(gamma)RIIB-deficient mice results from strain-specific epistasis. Immunity. 2000; 13 2: 277–285.
  • McGaha TL, Sorrentino B, Ravetch JV. Restoration of tolerance in lupus by targeted inhibitory receptor expression. Science. 2005; 307:590–593.
  • Floto RA, Clatworthy MR, Heilbronn KR, Rosner DR, MacAry PA, Rankin A, Lehner PJ, Ouwehand WH, Allen JM, Watkins NA, Smith KG. Loss of function of a lupus-associated FcgammaRIIb polymorphism through exclusion from lipid rafts. Nat Med. 2005; 11:1056–1058.
  • Mackay M, Stanevsky A, Wang T, Aranow C, Li M, Koenig S, Ravetch JV, Diamond B. Selective dysregulation of the FcgammaIIB receptor on memory B cells in SLE. J Exp Med. 2006; 203:2157–2164.
  • Chu SY, Vostiar I, Karki S, Moore GL, Lazar GA, Pong E, Joyce PF, Szymkowski DE, Desjarlais JR. Inhibition of B cell receptor-mediated activation of primary human B cells by coengagement of CD19 and FcgammaRIIb with Fc-engineered antibodies. Mol Immunol. 2008; 45:3926–3933.

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