279
Views
21
CrossRef citations to date
0
Altmetric
Research Article

B cells as effectors and regulators of sex-biased arthritis

, &
Pages 364-376 | Received 15 Jan 2012, Accepted 07 Feb 2012, Published online: 20 Mar 2012

References

  • Cariappa A, Chase C, Liu H, Russell P, Pillai S. Naive recirculating B cells mature simultaneously in the spleen and bone marrow. Blood. 2007; 109:2339–2345.
  • Lindsley RC, Thomas M, Srivastava B, Allman D. Generation of peripheral B cells occurs via two spatially and temporally distinct pathways. Blood. 2007; 109:2521–2528.
  • Allman D, Pillai S. Peripheral B cell subsets. Curr Opin Immunol. 2008; 20:149–157.
  • Carvalho TL, Mota-Santos T, Cumano A, Demengeot J, Vieira P. Arrested B lymphopoiesis and persistence of activated B cells in adult interleukin 7( − / − ) mice. J Exper Med. 2001; 194:1141–1150.
  • Hao Z, Rajewsky K. Homeostasis of peripheral B cells in the absence of B cell influx from the bone marrow. J Exper Med. 2001; 194:1151–1164.
  • Agenes F, Freitas AA. Transfer of small resting B cells into immunodeficient hosts results in the selection of a self-renewing activated B cell population. J Exper Med. 1999; 189:319–330.
  • Medina KL, Kincade PW. Pregnancy-related steroids are potential negative regulators of B lymphopoiesis. Proc Natl Acad Sci USA. 1994; 91:5382–5386.
  • Medina KL, Smithson G, Kincade PW. Suppression of B lymphopoiesis during normal pregnancy. J Exper Med. 1993; 178:1507–1515.
  • Pillai S, Mattoo H, Cariappa A. B cells and autoimmunity. Curr Opin Immunol23:721–731.
  • Meffre E, Wardemann H. B-cell tolerance checkpoints in health and autoimmunity. Curr Opin Immunol. 2008; 20:632–638.
  • Mountz J. Animal models of systemic lupus erythematosus and Sjogren's syndrome. Curr Opin Rheumatol. 1990; 2:740–748.
  • Tengstrand B, Ahlmen M, Hafstrom I. The influence of sex on rheumatoid arthritis: a prospective study of onset and outcome after 2 years. J Rheumatol. 2004; 31:214–222.
  • Sokka T, Toloza S, Cutolo M, Kautiainen H, Makinen H, Gogus F, . Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study. Arthritis Res Ther. 2009; 11:R7.
  • Ahlmen M, Svensson B, Albertsson K, Forslind K, Hafstrom I. Influence of gender on assessments of disease activity and function in early rheumatoid arthritis in relation to radiographic joint damage. Ann Rheum Dis. 2010; 69:230–233.
  • Atzeni F, Antivalle M, Pallavicini FB, Caporali R, Bazzani C, Gorla R, . Predicting response to anti-TNF treatment in rheumatoid arthritis patients. Autoimmun Rev. 2009; 8:431–437.
  • Gossec L, Baro-Riba J, Bozonnat MC, Daures JP, Sany J, Eliaou JF, . Influence of sex on disease severity in patients with rheumatoid arthritis. J Rheumatol. 2005; 32:1448–1451.
  • Stastny P. Association of the B-cell alloantigen DRw4 with rheumatoid arthritis. New Engl J Med. 1978; 298:869–871.
  • Winchester R, Dwyer E, Rose S. The genetic basis of rheumatoid arthritis. The shared epitope hypothesis. Rheumat Dis Clin N Amer. 1992; 18:761–783.
  • Stephens HA, Sakkas LI, Vaughan RW, Teitsson I, Welsh KI, Panayi GS. HLA-DQw7 is a disease severity marker in patients with rheumatoid arthritis. Immunogenetics. 1989; 30:119–122.
  • Taneja V, Mehra NK, Chandershekaran AN, Ahuja RK, Singh YN, Malaviya AN. HLA-DR4-DQw8, but not DR4-DQw7 haplotypes occur in Indian patients with rheumatoid arthritis. Rheumatol Inter. 1992; 11:251–255.
  • Gonzalez-Quintial R, Baccala R, Pope RM, Theofilopoulos AN. Identification of clonally expanded T cells in rheumatoid arthritis using a sequence enrichment nuclease assay. J Clin Invest. 1996; 97:1335–1343.
  • Strober S, Holoshitz J. Mechanisms of immune injury in rheumatoid arthritis: evidence for the involvement of T cells and heat-shock protein. Immunol Rev. 1990; 118:233–255.
  • Kim HJ, Krenn V, Steinhauser G, Berek C. Plasma cell development in synovial germinal centers in patients with rheumatoid and reactive arthritis. J Immunol. 1999; 162:3053–3062.
  • Van Boxel JA, Paget SA. Predominantly T-cell infiltrate in rheumatoid synovial membranes. New Engl J Med. 1975; 293:517–520.
  • Silverman GJ, Carson DA. Roles of B cells in rheumatoid arthritis. Arth Res Ther. 2003; 5 Suppl 4:S1–S6.
  • Bazzoni F, Beutler B. The tumor necrosis factor ligand and receptor families. New Engl J Med. 1996; 334:1717–1725.
  • Panayi GS. B cells: a fundamental role in the pathogenesis of rheumatoid arthritis?. Rheumatology (Oxford, England). 2005; 44 Suppl 2:ii3–ii7.
  • Vidard L, Kovacsovics-Bankowski M, Kraeft SK, Chen LB, Benacerraf B, Rock KL. Analysis of MHC class II presentation of particulate antigens of B lymphocytes. J Immunol. 1996; 156:2809–2818.
  • Wagner U, Kaltenhauser S, Pierer M, Wilke B, Arnold S, Hantzschel H. B lymphocytopenia in rheumatoid arthritis is associated with the DRB1 shared epitope and increased acute phase response. Arthritis Res. 2002; 4:R1.
  • Szodoray P, Alex P, Frank MB, Turner M, Turner S, Knowlton N, . A genome-scale assessment of peripheral blood B-cell molecular homeostasis in patients with rheumatoid arthritis. Rheumatology (Oxford, England). 2006; 45:1466–1476.
  • Huston MM, Moore JP, Mettes HJ, Tavana G, Huston DP. Human B cells express IL-5 receptor messenger ribonucleic acid and respond to IL-5 with enhanced IgM production after mitogenic stimulation with Moraxella catarrhalis. J Immunol. 1996; 156:1392–1401.
  • Mosmann T. Complexity or coherence?. Cytokine secretion by B cells. Nature Immunol. 2000; 1:465–466.
  • Henneken M, Dorner T, Burmester GR, Berek C. Differential expression of chemokine receptors on peripheral blood B cells from patients with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Res Ther. 2005; 7:R1001–R1013.
  • Dorner T, Burmester GR. The role of B cells in rheumatoid arthritis: mechanisms and therapeutic targets. Curr Opin Rheumatol. 2003; 15:246–252.
  • Takemura S, Klimiuk PA, Braun A, Goronzy JJ, Weyand CM. T cell activation in rheumatoid synovium is B cell dependent. J Immunol. 2001; 167:4710–4718.
  • Lesley R, Xu Y, Kalled SL, Hess DM, Schwab SR, Shu HB, . 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, . 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.
  • Bombardieri M, Kam NW, Brentano F, Choi K, Filer A, Kyburz D, . A BAFF/APRIL-dependent TLR3-stimulated pathway enhances the capacity of rheumatoid synovial fibroblasts to induce AID expression and Ig class-switching in B cells. Ann Rheumat dDis70:1857–1865.
  • Groom J, Kalled SL, Cutler AH, Olson C, Woodcock SA, Schneider P, . Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjogren's syndrome. J Clin Invest. 2002; 109:59–68.
  • Serreze DV, Fleming SA, Chapman HD, Richard SD, Leiter EH, Tisch RM. B lymphocytes are critical antigen-presenting cells for the initiation of T cell-mediated autoimmune diabetes in nonobese diabetic mice. J Immunol. 1998; 161:3912–3918.
  • Matsumoto I, Maccioni M, Lee DM, Maurice M, Simmons B, Brenner M, . How antibodies to a ubiquitous cytoplasmic enzyme may provoke joint-specific autoimmune disease. Nature Immunol. 2002; 3:360–365.
  • Chan OT, Madaio MP, Shlomchik MJ. The central and multiple roles of B cells in lupus pathogenesis. Immunol Rev. 1999; 169:107–121.
  • Svensson L, Jirholt J, Holmdahl R, Jansson L. B cell-deficient mice do not develop type II collagen-induced arthritis (CIA). Clin Exper Immunol. 1998; 111:521–526.
  • He X, Kang AH, Stuart JM. Accumulation of T cells reactive to type II collagen in synovial fluid of patients with rheumatoid arthritis. J Rheumatol. 2000; 27:589–593.
  • Andriopoulos NA, Mestecky J, Miller EJ, Bradley EL. Antibodies to native and denatured collagens in sera of patients with rheumatoid arthritis. Arthritis Rheumat. 1976; 19:613–617.
  • Clague RB, Shaw MJ, Holt PJ. Incidence of serum antibodies to native type I and type II collagens in patients with inflammatory arthritis. Ann Rheumatic Dis. 1980; 39:201–206.
  • Londei M, Savill CM, Verhoef A, Brennan F, Leech ZA, Duance V, . Persistence of collagen type II-specific T-cell clones in the synovial membrane of a patient with rheumatoid arthritis. Proc Natl Acad Sci USA. 1989; 86:636–640.
  • Tarkowski A, Klareskog L, Carlsten H, Herberts P, Koopman WJ. Secretion of antibodies to types I and II collagen by synovial tissue cells in patients with rheumatoid arthritis. Arthritis Rheumat. 1989; 32:1087–1092.
  • Taneja V, David CS. Role of HLA class II genes in susceptibility/resistance to inflammatory arthritis: studies with humanized mice. Immunol Rev233:62–78.
  • Brand DD, Kang AH, Rosloniec EF. Immunopathogenesis of collagen arthritis. Springer Sem Immunopathol. 2003; 25:3–18.
  • Bajtner E, Nandakumar KS, Engstrom A, Holmdahl R. Chronic development of collagen-induced arthritis is associated with arthritogenic antibodies against specific epitopes on type II collagen. Arthritis Res Ther. 2005; 7:R1148–R1157.
  • Dobritzsch D, Lindh I, Uysal H, Nandakumar KS, Burkhardt H, Schneider G, . Crystal structure of an arthritogenic anticollagen immune complex. Arthritis Rheumat63:3740–3748.
  • Wooley PH, Luthra HS, Singh SK, Huse AR, Stuart JM, David CS. Passive transfer of arthritis to mice by injection of human anti-type II collagen antibody. Mayo Clinic Proc. 1984; 59:737–743.
  • Mullazehi M, Mathsson L, Lampa J, Ronnelid J. High anti-collagen type-II antibody levels and induction of proinflammatory cytokines by anti-collagen antibody-containing immune complexes in vitro characterise a distinct rheumatoid arthritis phenotype associated with acute inflammation at the time of disease onset. Ann Rheumat Dis. 2007; 66:537–541.
  • 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.
  • 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.
  • Shlomchik MJ, Craft JE, Mamula MJ. From T to B and back again: positive feedback in systemic autoimmune disease. Nature Rev. 2001; 1:147–153.
  • Yan J, Harvey BP, Gee RJ, Shlomchik MJ, Mamula MJ. B cells drive early T cell autoimmunity in vivo prior to dendritic cell-mediated autoantigen presentation. J Immunol. 2006; 177:4481–4487.
  • Frey O, Bruns L, Morawietz L, Dunussi-Joannopoulos K, Kamradt T. B cell depletion reduces the number of autoreactive T helper cells and prevents glucose-6-phosphate isomerase-induced arthritis. PloS one6:e24718.
  • Amigorena S, Lankar D, Briken V, Gapin L, Viguier M, Bonnerot C. Type II and III receptors for immunoglobulin G (IgG) control the presentation of different T cell epitopes from single IgG-complexed antigens. J Exp Med. 1998; 187:505–515.
  • Hamano Y, Arase H, Saisho H, Saito T. Immune complex and Fc receptor-mediated augmentation of antigen presentation for in vivo Th cell responses. J Immunol. 2000; 164:6113–6119.
  • Hamel KM, Cao Y, Ashaye S, Wang Y, Dunn R, Kehry MR, . B cell depletion enhances T regulatory cell activity essential in the suppression of arthritis. J Immunol187:4900–4906.
  • Hamel K, Doodes P, Cao Y, Wang Y, Martinson J, Dunn R, . Suppression of proteoglycan-induced arthritis by anti-CD20 B Cell depletion therapy is mediated by reduction in autoantibodies and CD4+T cell reactivity. J Immunol. 2008; 180:4994–5003.
  • Kyburz D, Corr M, The KRN. mouse model of inflammatory arthritis. Springer Sem immunopathol. 2003; 25:79–-90.
  • Shih FF, Racz J, Allen PM. Differential MHC class II presentation of a pathogenic autoantigen during health and disease. J Immunol. 2006; 176:3438–3448.
  • Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P, . Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999; 190:1697–1710.
  • Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, . BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med. 1999; 189:1747–1756.
  • Zhang M, Ko KH, Lam QL, Lo CK, Srivastava G, Zheng B, . Expression and function of TNF family member B cell-activating factor in the development of autoimmune arthritis. Int Immunol. 2005; 17:1081–1092.
  • Gross JA, Dillon SR, Mudri S, Johnston J, Littau A, Roque R, . TACI-Ig neutralizes molecules critical for B cell development and autoimmune disease. impaired B cell maturation in mice lacking BLyS. Immunity. 2001; 15:289–302.
  • Liu Y, Zhang L, Wu Y, Tong T, Zhao W, Li P, . Therapeutic effects of TACI-Ig on collagen-induced arthritis by regulating T and B lymphocytes function in DBA/1 mice. Euro J Pharmacol654:304–314.
  • Lai Kwan Lam Q, King Hung Ko O, Zheng BJ, Lu L. Local BAFF gene silencing suppresses Th17-cell generation and ameliorates autoimmune arthritis. Proc Natl Acad Sci USA. 2008; 105:14993–14998.
  • Nabozny GH, Baisch JM, Cheng S, Cosgrove D, Griffiths MM, Luthra HS, . HLA-DQ8 transgenic mice are highly susceptible to collagen-induced arthritis: a novel model for human polyarthritis. J Exp Med. 1996; 183:27–37.
  • Taneja V, Hansen J, Smart M, Griffiths M, Luthra H, David CS. Expression of the H2-E molecule mediates protection to collagen-induced arthritis in HLA-DQ8 transgenic mice: role of cytokines. Int Immunol. 1997; 9:1213–1219.
  • Behrens M, Smart M, Luckey D, Luthra H, Taneja V. To B or not to B: role of B cells in pathogenesis of arthritis in HLA transgenic mice. J Autoimmun37:95–103.
  • Taneja V, Taneja N, Behrens M, Griffiths MM, Luthra HS, David CS. Requirement for CD28 may not be absolute for collagen-induced arthritis: study with HLA-DQ8 transgenic mice. J Immunol. 2005; 174:1118–1125.
  • Taneja V, Taneja N, Paisansinsup T, Behrens M, Griffiths M, Luthra H, . CD4 and CD8 T cells in susceptibility/protection to collagen-induced arthritis in HLA-DQ8-transgenic mice: implications for rheumatoid arthritis. J Immunol. 2002; 168:5867–5875.
  • Bradley DS, Nabozny GH, Cheng S, Zhou P, Griffiths MM, Luthra HS, . HLA-DQB1 polymorphism determines incidence, onset, and severity of collagen-induced arthritis in transgenic mice. Implications in human rheumatoid arthritis. J Clin Invest. 1997; 100:2227–2234.
  • Herlands RA, Christensen SR, Sweet RA, Hershberg U, Shlomchik MJ. T cell-independent and toll-like receptor-dependent antigen-driven activation of autoreactive B cells. Immunity. 2008; 29:249–260.
  • 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.
  • 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.
  • Liljander M, Andersson A, Holmdahl R, Mattsson R. Increased susceptibility to collagen-induced arthritis in female mice carrying congenic Cia40/Pregq2 fragments. Arthritis Res Ther. 2008; 10:R88.
  • van Beuningen HM, van den Berg WB, Schalkwijk J, Arntz OJ, van de Putte LB. Age- and sex-related differences in antigen-induced arthritis in C57Bl/10 mice. Arthritis Rheumat. 1989; 32:789–794.
  • Jansson L, Holmdahl R. Genes on the X chromosome affect development of collagen-induced arthritis in mice. Clin Exper immunol. 1993; 94:459–465.
  • Scotland RS, Stables MJ, Madalli S, Watson P, Gilroy DW. Sex differences in resident immune cell phenotype underlie more efficient acute inflammatory responses in female mice. Blood118:5918–5927.
  • Rosloniec EF, Brand DD, Myers LK, Esaki Y, Whittington KB, Zaller DM, . Induction of autoimmune arthritis in HLA-DR4 (DRB1*0401) transgenic mice by immunization with human and bovine type II collagen. J Immunol. 1998; 160:2573–2578.
  • Whitacre CC, Reingold SC, O'Looney PA. A gender gap in autoimmunity. Science. 1999; 283:1277–1278.
  • Behrens M, Trejo T, Luthra H, Griffiths M, David CS, Taneja V. Mechanism by which HLA-DR4 regulates sex-bias of arthritis in humanized mice. J Autoimmun35:1–9.
  • Tsark EC, Wang W, Teng YC, Arkfeld D, Dodge GR, Kovats S. Differential MHC class II-mediated presentation of rheumatoid arthritis autoantigens by human dendritic cells and macrophages. J Immunol. 2002; 169:6625–6633.
  • Duncan DD, Swain SL. Role of antigen-presenting cells in the polarized development of helper T cell subsets: evidence for differential cytokine production by Th0 cells in response to antigen presentation by B cells and macrophages. Euro J Immunol. 1994; 24:2506–2514.
  • Minty A, Chalon P, Derocq JM, Dumont X, Guillemot JC, Kaghad M, . Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature. 1993; 362:248–250.
  • Kinloch AJ, Lundberg KE, Moyes D, Venables PJ. Pathogenic role of antibodies to citrullinated proteins in rheumatoid arthritis. Expert Rev Clin Immunol. 2006; 2:365–375.
  • Senshu T, Akiyama K, Nagata S, Watanabe K, Hikichi K. Peptidylarginine deiminase in rat pituitary: sex difference, estrous cycle-related changes, and estrogen dependence. Endocrinology. 1989; 124:2666–2670.
  • van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Huizinga TW, Toes RE, de Vries RR. The HLA-DRB1 shared epitope alleles are primarily a risk factor for anti-cyclic citrullinated peptide antibodies and are not an independent risk factor for development of rheumatoid arthritis. Arthritis Rheumat. 2006; 54:1117–1121.
  • Hill JA, Southwood S, Sette A, Jevnikar AM, Bell DA, Cairns E. Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule. J Immunol. 2003; 171:538–541.
  • Cutolo M. Sex and rheumatoid arthritis: mouse model versus human disease. Arthritis Rheumat. 2007; 56:1–3.
  • de Man YA, Bakker-Jonges LE, Goorbergh CM, Tillemans SP, Hooijkaas H, Hazes JM, . Women with rheumatoid arthritis negative for anti-cyclic citrullinated peptide and rheumatoid factor are more likely to improve during pregnancy, whereas in autoantibody-positive women autoantibody levels are not influenced by pregnancy. Ann Rheumat Dis69:420–423.
  • Kanda N, Tamaki K. Estrogen enhances immunoglobulin production by human PBMCs. J Allergy Clin Immunol. 1999; 103:282–288.
  • Rowley MJ, Mackay IR. Measurement of antibody-producing capacity in man. I. The normal response to flagellin from Salmonella adelaide. Clin Exper immunol. 1969; 5:407–418.
  • Grimaldi CM, Cleary J, Dagtas AS, Moussai D, Diamond B. Estrogen alters thresholds for B cell apoptosis and activation. J Clin Invest. 2002; 109:1625–1633.
  • Cutolo M, Capellino S, Sulli A, Serioli B, Secchi ME, Villaggio B, . Estrogens and autoimmune diseases. Ann NY Acad Sci. 2006; 1089:538–547.
  • Grimaldi CM, Jeganathan V, Diamond B. Hormonal regulation of B cell development: 17 beta-estradiol impairs negative selection of high-affinity DNA-reactive B cells at more than one developmental checkpoint. J Immunol. 2006; 176:2703–2710.
  • Tengstrand B, Carlstrom K, Fellander-Tsai L, Hafstrom I. Abnormal levels of serum dehydroepiandrosterone, estrone, and estradiol in men with rheumatoid arthritis: high correlation between serum estradiol and current degree of inflammation. J Rheumatol. 2003; 30:2338–2343.
  • Jansson L, Holmdahl R. Estrogen-mediated immunosuppression in autoimmune diseases. Inflamm Res. 1998; 47:290–301.
  • Nalbandian G, Kovats S. Understanding sex biases in immunity: effects of estrogen on the differentiation and function of antigen-presenting cells. Immunol Res. 2005; 31:91–106.
  • Hill L, Jeganathan V, Chinnasamy P, Grimaldi C, Diamond B. Differential roles of estrogen receptors alpha and beta in control of B-cell maturation and selection. Mol Med17:211–220.
  • Medina KL, Strasser A, Kincade PW. Estrogen influences the differentiation, proliferation, and survival of early B-lineage precursors. Blood. 2000; 95:2059–2067.
  • Ellis TM, Moser MT, Le PT, Flanigan RC, Kwon ED. Alterations in peripheral B cells and B cell progenitors following androgen ablation in mice. Int Immunol. 2001; 13:553–558.
  • Engdahl C, Jochems C, Windahl SH, Borjesson AE, Ohlsson C, Carlsten H, . Amelioration of collagen-induced arthritis and immune-associated bone loss through signaling via estrogen receptor alpha, and not estrogen receptor beta or G protein-coupled receptor 30. Arthr Rheumat62:524–533.
  • Wira CR, Fahey JV, Abrahams VM, Rossoll RM. Influence of stage of the reproductive cycle and estradiol on thymus cell antigen presentation. J Ster Biochem Mol Biol. 2003; 84:79–87.
  • Linton PJ, Harbertson J, Bradley LM. A critical role for B cells in the development of memory CD4 cells. J Immunol. 2000; 165:5558–5565.
  • Harris DP, Haynes L, Sayles PC, Duso DK, Eaton SM, Lepak NM, . Reciprocal regulation of polarized cytokine production by effector B and T cells. Nature immunol. 2000; 1:475–482.
  • Lund FE, Garvy BA, Randall TD, Harris DP. Regulatory roles for cytokine-producing B cells in infection and autoimmune disease. Curr Direct autoimmun. 2005; 8:25–54.
  • Bouaziz JD, Yanaba K, Tedder TF. Regulatory B cells as inhibitors of immune responses and inflammation. Immunol Rev. 2008; 224:201–214.
  • Mauri C, Blair PA. Regulatory B cells in autoimmunity: developments and controversies. Nat Rev Rheumatol;6:636–643.
  • Fillatreau S, Gray D, Anderton SM. Not always the bad guys: B cells as regulators of autoimmune pathology. Nature Rev. 2008; 8:391–397.
  • Mauri C, Gray D, Mushtaq N, Londei M. Prevention of arthritis by interleukin 10-producing B cells. J Exp Med. 2003; 197:489–501.
  • Evans JG, Chavez-Rueda KA, Eddaoudi A, Meyer-Bahlburg A, Rawlings DJ, Ehrenstein MR, . Novel suppressive function of transitional 2 B cells in experimental arthritis. J Immunol. 2007; 178:7868–7878.
  • Gray M, Miles K, Salter D, Gray D, Savill J. Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory B cells. Proc Natl Acad Sci USA. 2007; 104:14080–14085.
  • Yanaba K, Bouaziz JD, Haas KM, Poe JC, Fujimoto M, Tedder TF. A regulatory B cell subset with a unique CD1dhiCD5+phenotype controls T cell-dependent inflammatory responses. Immunity. 2008; 28:639–650.
  • Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, . Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006; 54:2793–2806.
  • Emery P, Fleischmann R, Filipowicz-Sosnowska A, Schechtman J, Szczepanski L, Kavanaugh A, . The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthr Rheumat. 2006; 54:139–400.
  • Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, . Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004; 350:2572–2581.
  • Engel P, Gomez-Puerta JA, Ramos-Casals M, Lozano F, Bosch X. Therapeutic targeting of B cells for rheumatic autoimmune diseases. Pharmacol Rev63:127–156.
  • Cohen SB. Updates from B cell trials: Efficacy. J Rheumatol. 2006; 77:12–17.
  • Kavanaugh A, Rosengren S, Lee SJ, Hammaker D, Firestein GS, Kalunian K, . Assessment of rituximab's immunomodulatory synovial effects (ARISE trial). 1: clinical and synovial biomarker results. Ann Rheumat Dis. 2008; 67:402–408.
  • Yanaba K, Hamaguchi Y, Venturi GM, Steeber DA, St Clair EW, Tedder TF. B cell depletion delays collagen-induced arthritis in mice: arthritis induction requires synergy between humoral and cell-mediated immunity. J Immunol. 2007; 179:1369–1380.
  • Huang H, Benoist C, Mathis D. Rituximab specifically depletes short-lived autoreactive plasma cells in a mouse model of inflammatory arthritis. Proc Natl Acad Sci USA;107:4658–4663.
  • Khan S, Greenberg JD, Bhardwaj N. Dendritic cells as targets for therapy in rheumatoid arthritis. Nature Rev. 2009; 5:566–571.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.