B cells as effectors and regulators of autoimmunity

References

• Gomez-Martin D, Diaz-Zamudio M, Romo-Tena J, Ibarra-Sanchez MJ, Alcocer-Varela J. Follicular helper T cells poise immune responses to the development of autoimmune pathology. Autoimmun Rev. 2011; 10:325–330.
   Google Scholar
• Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Becker DJ, Gitelman SE, Goland R, Gottlieb PA, Marks JB, McGee PF, Moran AM, Raskin P, Rodriguez H, Schatz DA, Wherrett D, Wilson DM, Lachin JM, Skyler JS. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med. 2009; 361:2143–2152.
   PubMed Web of Science ®Google Scholar
• Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, Keystone EC, Loveless JE, Burmester GR, Cravets MW, Hessey EW, Shaw T, Totoritis 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.
   PubMed Web of Science ®Google Scholar
• Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008; 358:676–688.
   PubMed Web of Science ®Google Scholar
• Liossis SN, Sfikakis PP. Rituximab-induced B cell depletion in autoimmune diseases: potential effects on T cells. Clin Immunol. 2008; 127:280–285.
   PubMed Web of Science ®Google Scholar
• Tisch R, McDevitt H. Insulin-dependent diabetes mellitus. Cell. 1996; 85:291–297.
   PubMed Web of Science ®Google Scholar
• Gepts W. Pathologic anatomy of the pancreas in juvenile diabetes mellitus. Diabetes. 1965; 14:619–633.
   PubMed Web of Science ®Google Scholar
• Foulis AK, Stewart JA. The pancreas in recent-onset type 1 (insulin-dependent) diabetes mellitus: insulin content of islets, insulitis and associated changes in the exocrine acinar tissue. Diabetologia. 1984; 26:456–461.
   PubMed Web of Science ®Google Scholar
• Somoza N, Vargas F, Roura-Mir C, Vives-Pi M, Fernandez-Figueras MT, Ariza A, Gomis R, Bragado R, Marti M, Jaraquemada D, . Pancreas in recent onset insulin-dependent diabetes mellitus. Changes in HLA, adhesion molecules and autoantigens, restricted T cell receptor V beta usage, and cytokine profile. J Immunol. 1994; 153:1360–1377.
   PubMed Web of Science ®Google Scholar
• Panina-Bordignon P, Lang R, van Endert PM, Benazzi E, Felix AM, Pastore RM, Spinas GA, Sinigaglia F. Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes. J Exp Med. 1995; 181:1923–1927.
   PubMed Web of Science ®Google Scholar
• Skowera A, Ellis RJ, Varela-Calvino R, Arif S, Huang GC, Van-Krinks C, Zaremba A, Rackham C, Allen JS, Tree TI, Zhao M, Dayan CM, Sewell AK, Unger WW, Drijfhout JW, Ossendorp F, Roep BO, Peakman M. CTLs are targeted to kill beta cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope. J Clin Invest. 2008; 118:3390–3402.
   PubMed Web of Science ®Google Scholar
• Coppieters KT, Dotta F, Amirian N, Campbell PD, Kay TW, Atkinson MA, Roep BO, von Herrath MG. Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. J Exp Med 2012.
   Google Scholar
• Wong FS, Karttunen J, Dumont C, Wen L, Visintin I, Pilip IM, Shastri N, Pamer EG, Janeway CAJr. Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library. Nat Med. 1999; 5:1026–1031.
   PubMed Web of Science ®Google Scholar
• Stadinski BD, Delong T, Reisdorph N, Reisdorph R, Powell RL, Armstrong M, Piganelli JD, Barbour G, Bradley B, Crawford F, Marrack P, Mahata SK, Kappler JW, Haskins K, Chromogranin A. A is an autoantigen in type 1 diabetes. Nat Immunol. 2010; 11:225–231.
   PubMed Web of Science ®Google Scholar
• Roep BO, Atkinson M, von Herrath M. Satisfaction (not) guaranteed: re-evaluating the use of animal models of type 1 diabetes. Nat Rev Immunol. 2004; 4:989–997.
   PubMedGoogle Scholar
• Nejentsev S, Howson JM, Walker NM, Szeszko J, Field SF, Stevens HE, Reynolds P, Hardy M, King E, Masters J, Hulme J, Maier LM, Smyth D, Bailey R, Cooper JD, Ribas G, Campbell RD, Clayton DG, Todd JA. Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A. Nature. 2007; 450:887–892.
   PubMed Web of Science ®Google Scholar
• Lampeter EF, Homberg M, Quabeck K, Schaefer UW, Wernet P, Bertrams J, Grosse-Wilde H, Gries FA, Kolb H. Transfer of insulin-dependent diabetes between HLA-identical siblings by bone marrow transplantation. Lancet. 1993; 341:1243–1244.
   PubMed Web of Science ®Google Scholar
• Exner BG, Groninger JH, Ildstad ST. Bone marrow transplantation for therapy in autoimmune disease. Stem Cells. 1997; 15 Suppl 1: 171–175 discussion 175–6.
   Google Scholar
• Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, Bluestone JA. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med. 2002; 346:1692–1698.
   PubMed Web of Science ®Google Scholar
• Feutren G, Papoz L, Assan R, Vialettes B, Karsenty G, Vexiau P, Du Rostu H, Rodier M, Sirmai J, Lallemand A, . Cyclosporin increases the rate and length of remissions in insulin-dependent diabetes of recent onset. Results of a multicentre double-blind trial. Lancet. 1986; 2:119–124.
   PubMed Web of Science ®Google Scholar
• Marino E, Silveira PA, Stolp J, Grey ST. B cell-directed therapies in type 1 diabetes. Trends Immunol. 2011; 32:287–294.
   PubMed Web of Science ®Google Scholar
• Taylor RP, Lindorfer MA. Immunotherapeutic mechanisms of anti-CD20 monoclonal antibodies. Curr Opin Immunol. 2008; 20:444–449.
   PubMed Web of Science ®Google Scholar
• Martin S, Wolf-Eichbaum D, Duinkerken G, Scherbaum WA, Kolb H, Noordzij JG, Roep BO. Development of type 1 diabetes despite severe hereditary B-lymphocyte deficiency. N Engl J Med. 2001; 345:1036–1040.
   PubMed Web of Science ®Google Scholar
• Silveira PA, Grey ST. B cells in the spotlight: innocent bystanders or major players in the pathogenesis of type 1 diabetes. Trends Endocrinol Metab. 2006; 17:128–135.
   PubMed Web of Science ®Google Scholar
• Bottazzo GF, Dean BM, McNally JM, MacKay EH, Swift PG, Gamble DR. In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med. 1985; 313:353–360.
   PubMed Web of Science ®Google Scholar
• MacCuish AC, Irvine WJ, Barnes EW, Duncan LJ. Antibodies to pancreatic islet cells in insulin-dependent diabetics with coexistent autoimmune disease. Lancet. 1974; 2:1529–1531.
   PubMedGoogle Scholar
• Miao D, Yu L, Eisenbarth GS. Role of autoantibodies in type 1 diabetes. Front Biosci. 2007; 12:1889–1898.
   PubMedGoogle Scholar
• Verge CF, Gianani R, Kawasaki E, Yu L, Pietropaolo M, Jackson RA, Chase HP, Eisenbarth GS. Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes. 1996; 45:926–933.
   PubMed Web of Science ®Google Scholar
• Bingley PJ, Christie MR, Bonifacio E, Bonfanti R, Shattock M, Fonte MT, Bottazzo GF, Gale EA. Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives. Diabetes. 1994; 43:1304–1310.
   PubMed Web of Science ®Google Scholar
• Signore A, Pozzilli P, Gale EA, Andreani D, Beverley PC. The natural history of lymphocyte subsets infiltrating the pancreas of NOD mice. Diabetologia. 1989; 32:282–289.
   PubMed Web of Science ®Google Scholar
• Goldrath AW, Barber L, Chen KE, Alters SE. Differences in adhesion markers, activation markers, and TcR in islet infiltrating vs. peripheral lymphocytes in the NOD mouse. J Autoimmun. 1995; 8:209–220.
   PubMed Web of Science ®Google Scholar
• Faveeuw C, Gagnerault MC, Kraal G, Lepault F. Homing of lymphocytes into islets of Langerhans in prediabetic non-obese diabetic mice is not restricted to autoreactive T cells. Int Immunol. 1995; 7:1905–1913.
   Google Scholar
• Puertas MC, Carrillo J, Pastor X, Ampudia RM, Alba A, Planas R, Pujol-Borrell R, Vives-Pi M, Verdaguer J. Phenotype and functional characteristics of islet-infiltrating B-cells suggest the existence of immune regulatory mechanisms in islet milieu. Diabetes. 2007; 56:940–949.
   Google Scholar
• Marino E, Batten M, Groom J, Walters S, Liuwantara D, Mackay F, Grey ST. Marginal-zone B-cells of nonobese diabetic mice expand with diabetes onset, invade the pancreatic lymph nodes, and present autoantigen to diabetogenic T-cells. Diabetes. 2008; 57:395–404.
   PubMed Web of Science ®Google Scholar
• Serreze DV, Chapman HD, Varnum DS, Hanson MS, Reifsnyder PC, Richard SD, Fleming SA, Leiter EH, Shultz LD. B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new “speed congenic” stock of NOD.Ig mu null mice. J Exp Med. 1996; 184:2049–2053.
   PubMed Web of Science ®Google Scholar
• Akashi T, Nagafuchi S, Anzai K, Kondo S, Kitamura D, Wakana S, Ono J, Kikuchi M, Niho Y, Watanabe T. Direct evidence for the contribution of B cells to the progression of insulitis and the development of diabetes in non-obese diabetic mice. Int Immunol. 1997; 9:1159–1164.
   PubMed Web of Science ®Google Scholar
• Kitamura D, Roes J, Kuhn R, Rajewsky K. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene. Nature. 1991; 350:423–426.
   PubMed Web of Science ®Google Scholar
• Greeley SA, Moore DJ, Noorchashm H, Noto LE, Rostami SY, Schlachterman A, Song HK, Koeberlein B, Barker CF, Naji A. Impaired activation of islet-reactive CD4 T cells in pancreatic lymph nodes of B cell-deficient nonobese diabetic mice. J Immunol. 2001; 167:4351–4357.
   PubMed Web of Science ®Google Scholar
• Wong FS, Wen L, Tang M, Ramanathan M, Visintin I, Daugherty J, Hannum LG, Janeway CAJr, Shlomchik MJ. Investigation of the role of B-cells in type 1 diabetes in the NOD mouse. Diabetes. 2004; 53:2581–2587.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Forsgren S, Andersson A, Hillorn V, Soderstrom A, Holmberg D. Immunoglobulin-mediated prevention of autoimmune diabetes in the non-obese diabetic (NOD) mouse. Scand J Immunol. 1991; 34:445–451.
   PubMed Web of Science ®Google Scholar
• Noorchashm H, Noorchashm N, Kern J, Rostami SY, Barker CF, Naji A. B-cells are required for the initiation of insulitis and sialitis in nonobese diabetic mice. Diabetes. 1997; 46:941–946.
   PubMed Web of Science ®Google Scholar
• Hu CY, Rodriguez-Pinto D, Du W, Ahuja A, Henegariu O, Wong FS, Shlomchik MJ, Wen L. Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. J Clin Invest. 2007; 117:3857–3867.
   PubMed Web of Science ®Google Scholar
• Xiu Y, Wong CP, Bouaziz JD, Hamaguchi Y, Wang Y, Pop SM, Tisch RM, Tedder TF. B lymphocyte depletion by CD20 monoclonal antibody prevents diabetes in nonobese diabetic mice despite isotype-specific differences in FcgammaR effector functions. J Immunol. 2008; 180:2863–2875.
   PubMed Web of Science ®Google Scholar
• Fiorina P, Vergani A, Dada S, Jurewicz M, Wong M, Law K, Wu E, Tian Z, Abdi R, Guleria I, Rodig S, Dunussi-Joannopoulos K, Bluestone J, Sayegh MH. Targeting CD22 reprograms B cells and reverses autoimmune diabetes. Diabetes 2008.
   Google Scholar
• Zekavat G, Rostami SY, Badkerhanian A, Parsons RF, Koeberlein B, Yu M, Ward CD, Migone TS, Yu L, Eisenbarth GS, Cancro MP, Naji A, Noorchashm H. In vivo BLyS/BAFF neutralization ameliorates islet-directed autoimmunity in nonobese diabetic mice. J Immunol. 2000; 181:8133–8144.
   Google Scholar
• Marino E, Villanueva J, Walters S, Liuwantara D, Mackay F. Grey ST: CD4(+)CD25(+) T-cells control autoimmunity in the absence of B-cells. Diabetes. 2009; 58:1568–1577.
   PubMed Web of Science ®Google Scholar
• Mackay F, Sierro F, Grey ST, Gordon TP. The BAFF/APRIL system: an important player in systemic rheumatic diseases. Curr Dir Autoimmun. 2005; 8:243–265.
   PubMedGoogle Scholar
• Bonifacio E, Atkinson M, Eisenbarth G, Serreze D, Kay TW, Lee-Chan E, Singh B. International Workshop on Lessons From Animal Models for Human Type 1 Diabetes: identification of insulin but not glutamic acid decarboxylase or IA-2 as specific autoantigens of humoral autoimmunity in nonobese diabetic mice. Diabetes. 2001; 50:2451–2458.
   PubMed Web of Science ®Google Scholar
• Harbers SO, Crocker A, Catalano G, D'Agati V, Jung S, Desai DD, Clynes R. Antibody-enhanced cross-presentation of self antigen breaks T cell tolerance. J Clin Invest. 2007; 117:1361–1369.
   PubMedGoogle Scholar
• Inoue Y, Kaifu T, Sugahara-Tobinai A, Nakamura A, Miyazaki J, Takai T. Activating Fc gamma receptors participate in the development of autoimmune diabetes in NOD mice. J Immunol. 2007; 179:764–774.
   PubMed Web of Science ®Google Scholar
• Silva DG, Daley SR, Hogan J, Lee SK, Teh CE, Hu DY, Lam KP, Goodnow CC, Vinuesa CG. Anti-islet autoantibodies trigger autoimmune diabetes in the presence of an increased frequency of islet-reactive CD4 T cells. Diabetes. 2011; 60:2102–2111.
   Google Scholar
• Greeley SA, Katsumata M, Yu L, Eisenbarth GS, Moore DJ, Goodarzi H, Barker CF, Naji A, Noorchashm H. Elimination of maternally transmitted autoantibodies prevents diabetes in nonobese diabetic mice. Nat Med. 2002; 8:399–402.
   PubMed Web of Science ®Google Scholar
• Koczwara K, Ziegler AG, Bonifacio E. Maternal immunity to insulin does not affect diabetes risk in progeny of non obese diabetic mice. Clin Exp Immunol. 2004; 136:56–59.
   PubMedGoogle Scholar
• Koczwara K, Bonifacio E, Ziegler AG. Transmission of maternal islet antibodies and risk of autoimmune diabetes in offspring of mothers with type 1 diabetes. Diabetes. 2004; l53:1–4.
   Google Scholar
• Genain CP, Cannella B, Hauser SL, Raine CS. Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat Med. 1999; 5:170–175.
   PubMed Web of Science ®Google Scholar
• Genain CP, Nguyen MH, Letvin NL, Pearl R, Davis RL, Adelman M, Lees MB, Linington C, Hauser SL. Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate. J Clin Invest. 1995; 96:2966–2974.
   PubMedGoogle Scholar
• Green EA, Eynon EE, Flavell RA. Local expression of TNFalpha in neonatal NOD mice promotes diabetes by enhancing presentation of islet antigens. Immunity. 1998; 9:733–743.
   PubMed Web of Science ®Google Scholar
• Green EA, Wong FS, Eshima K, Mora C, Flavell RA. Neonatal tumor necrosis factor alpha promotes diabetes in nonobese diabetic mice by CD154-independent antigen presentation to CD8(+) T cells. J Exp Med. 2000; 191:225–238.
   PubMed Web of Science ®Google Scholar
• Brodie GM, Wallberg M, Santamaria P, Wong FS, Green EA. B cells promote intra-islet CD8+cytotoxic T lymphocyte survival to enhance type 1 diabetes. Diabetes 2008.
   Google Scholar
• Falcone M, Lee J, Patstone G, Yeung B, Sarvetnick N. B lymphocytes are crucial antigen-presenting cells in the pathogenic autoimmune response to GAD65 antigen in nonobese diabetic mice. J Immunol. 1998; 161:1163–1168.
   PubMed Web of Science ®Google Scholar
• Noorchashm H, Lieu YK, Noorchashm N, Rostami SY, Greeley SA, Schlachterman A, Song HK, Noto LE, Jevnikar AM, Barker CF, Naji A. I-Ag7-mediated antigen presentation by B lymphocytes is critical in overcoming a checkpoint in T cell tolerance to islet beta cells of nonobese diabetic mice. J Immunol. 1999; 163:743–750.
   PubMed Web of Science ®Google Scholar
• Katz JD, Wang B, Haskins K, Benoist C, Mathis D. Following a diabetogenic T cell from genesis through pathogenesis. Cell. 1993; 74:1089–1100.
   PubMed Web of Science ®Google Scholar
• Nakayama M, Beilke JN, Jasinski JM, Kobayashi M, Miao D, Li M, Coulombe MG, Liu E, Elliott JF, Gill RG, Eisenbarth GS. Priming and effector dependence on insulin B:9-23 peptide in NOD islet autoimmunity. J Clin Invest. 2007; 117:1835–1843.
   PubMed Web of Science ®Google Scholar
• Wheat W, Kupfer R, Gutches DG, Rayat GR, Beilke J, Scheinman RI, Wegmann DR. Increased NF-kappa B activity in B cells and bone marrow-derived dendritic cells from NOD mice. Eur J Immunol. 2004; 34:1395–1404.
   PubMed Web of Science ®Google Scholar
• LeBien TW, Tedder TF. B lymphocytes: how they develop and function. Blood. 2008; 112:1570–1580.
   PubMed Web of Science ®Google Scholar
• Nakayama M, Abiru N, Moriyama H, Babaya N, Liu E, Miao D, Yu L, Wegmann DR, Hutton JC, Elliott JF, Eisenbarth GS. Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature. 2005; 435:220–223.
   PubMed Web of Science ®Google Scholar
• Krishnamurthy B, Dudek NL, McKenzie MD, Purcell AW, Brooks AG, Gellert S, Colman PG, Harrison LC, Lew AM, Thomas HE, Kay TW. Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP. J Clin Invest. 2006; 116:3258–3265.
   PubMed Web of Science ®Google Scholar
• Tian J, Clare-Salzler M, Herschenfeld A, Middleton B, Newman D, Mueller R, Arita S, Evans C, Atkinson MA, Mullen Y, Sarvetnick N, Tobin AJ, Lehmann PV, Kaufman DL. Modulating autoimmune responses to GAD inhibits disease progression and prolongs islet graft survival in diabetes-prone mice. Nat Med. 1996; 2:1348–1353.
   PubMed Web of Science ®Google Scholar
• Amrani A, Verdaguer J, Serra P, Tafuro S, Tan R, Santamaria P. Progression of autoimmune diabetes driven by avidity maturation of a T-cell population. Nature. 2000; 406:739–742.
   PubMed Web of Science ®Google Scholar
• Tian J, Zekzer D, Lu Y, Dang H, Kaufman DL. B cells are crucial for determinant spreading of T cell autoimmunity among beta cell antigens in diabetes-prone nonobese diabetic mice. J Immunol. 2006; 176:2654–2661.
   PubMed Web of Science ®Google Scholar
• Kaufman DL, Clare-Salzler M, Tian J, Forsthuber T, Ting GS, Robinson P, Atkinson MA, Sercarz EE, Tobin AJ, Lehmann PV. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes. Nature. 1993; 366:69–72.
   PubMed Web of Science ®Google Scholar
• Tian J, Gregori S, Adorini L, Kaufman DL. The frequency of high avidity T cells determines the hierarchy of determinant spreading. J Immunol. 2001; 166:7144–7150.
   PubMed Web of Science ®Google Scholar
• Hoglund P, Mintern J, Waltzinger C, Heath W, Benoist C, Mathis D. Initiation of autoimmune diabetes by developmentally regulated presentation of islet cell antigens in the pancreatic lymph nodes. J Exp Med. 1999; 189:331–339.
   PubMed Web of Science ®Google Scholar
• Turley S, Poirot L, Hattori M, Benoist C, Mathis D. Physiological beta cell death triggers priming of self-reactive T cells by dendritic cells in a type-1 diabetes model. J Exp Med. 2003; 198:1527–1537.
   PubMed Web of Science ®Google Scholar
• Bouaziz JD, Yanaba K, Venturi GM, Wang Y, Tisch RM, Poe JC, Tedder TF. Tedder TF. Therapeutic B cell depletion impairs adaptive and autoreactive CD4+T cell activation in mice. Proc Natl Acad Sci USA. 2007; 104:20878–20883.
   PubMed Web of Science ®Google Scholar
• Villadangos JA, Schnorrer P. Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo. Nat Rev Immunol. 2007; 7:543–555.
   PubMed Web of Science ®Google Scholar
• Walters S, Webster KE, Sutherland A, Gardam S, Groom J, Liuwantara D, Marino E, Thaxton J, Weinberg A, Mackay F, Brink R, Sprent J, Grey ST. Increased CD4+Foxp3+T cells in BAFF-transgenic mice suppress T cell effector responses. J Immunol. 2009; 182:793–801.
   PubMedGoogle Scholar
• Epstein MM, Di Rosa F, Jankovic D, Sher A. Matzinger P. Successful T cell priming in B cell-deficient mice. J Exp Med. 1995; 182:915–922.
   Google Scholar
• Dahlen E, Dawe K, Ohlsson L, Hedlund G. Dendritic cells and macrophages are the first and major producers of TNF-alpha in pancreatic islets in the nonobese diabetic mouse. J Immunol. 1998; 160:3585–3593.
   PubMed Web of Science ®Google Scholar
• Serreze DV, Gaedeke JW, Leiter EH. Hematopoietic stem-cell defects underlying abnormal macrophage development and maturation in NOD/Lt mice: defective regulation of cytokine receptors and protein kinase C. Proc Natl Acad Sci USA. 1993; 90:9625–9629.
   PubMed Web of Science ®Google Scholar
• Vasquez AC, Feili-Hariri M, Tan RJ, Morel PA. Qualitative and quantitative abnormalities in splenic dendritic cell populations in NOD mice. Clin Exp Immunol. 2004; 135:209–218.
   PubMed Web of Science ®Google Scholar
• Litherland SA, Xie XT, Hutson AD, Wasserfall C, Whittaker DS, She JX, Hofig A, Dennis MA, Fuller K, Cook R, Schatz D, Moldawer LL, Clare-Salzler MJ. Aberrant prostaglandin synthase 2 expression defines an antigen-presenting cell defect for insulin-dependent diabetes mellitus. J Clin Invest. 1999; 104:515–523.
   PubMed Web of Science ®Google Scholar
• Jansen A, van Hagen M. Defective maturation and function of antigen-presenting cells in type 1 diabetes. Lancet. 1995; 345:491–492.
   PubMed Web of Science ®Google Scholar
• Takahashi K, Honeyman MC, Harrison LC. Impaired yield, phenotype, and function of monocyte-derived dendritic cells in humans at risk for insulin-dependent diabetes. J Immunol. 1998; 161:2629–2635.
   PubMed Web of Science ®Google Scholar
• Noorchashm H, Moore DJ, Noto LE, Noorchashm N, Reed AJ, Reed AL, Song HK, Mozaffari R, Jevnikar AM, Barker CF, Naji A. Impaired CD4 T cell activation due to reliance upon B cell-mediated costimulation in nonobese diabetic (NOD) mice. J Immunol. 2000; 165:4685–4696.
   PubMed Web of Science ®Google Scholar
• Hussain S, Delovitch TL. Dysregulated B7-1 and B7-2 expression on nonobese diabetic mouse B cells is associated with increased T cell costimulation and the development of insulitis. J Immunol. 2005; 174:680–687.
   PubMedGoogle Scholar
• Silveira PA, Dombrowsky J, Johnson E, Chapman HD, Nemazee D, Serreze DV. B cell selection defects underlie the development of diabetogenic APCs in nonobese diabetic mice. J Immunol. 2004; 172:5086–5094.
   PubMed Web of Science ®Google Scholar
• Thomas JW, Kendall PL, Mitchell HG. The natural autoantibody repertoire of nonobese diabetic mice is highly active. J Immunol. 2002; 169:6617–6624.
   PubMed Web of Science ®Google Scholar
• Habib T, Funk A, Rieck M, Brahmandam A, Dai X, Panigrahi AK, Luning Prak ET, Meyer-Bahlburg A, Sanda S, Greenbanm C, Rawlings DJ, Buckner JH. Altered B cell homeostasis is associated with Type I diabetes and carriers of the PTPN22 allelic variant. J Immunol. 2012; 188:487–496.
   Google Scholar
• Menard L, Saadoun D, Isnardi I, Ng YS, Meyers G, Massad C, Price C, Abraham C, Motaghedi R, Buckner JH, Gregersen PK, Meffre E. The PTPN22 allele encoding an R620W variant interferes with the removal of developing autoreactive B cells in humans. J Clin Invest. 2011; 121:3635–3644.
   PubMed Web of Science ®Google Scholar
• Panigrahi AK, Goodman NG, Eisenberg RA, Rickels MR, Naji A, Luning Prak ET. RS rearrangement frequency as a marker of receptor editing in lupus and type 1 diabetes. J Exp Med. 2008; 205:2985–2994.
   PubMed Web of Science ®Google Scholar
• Malynn BA, Romeo DT, Wortis HH. Antigen-specific B cells efficiently present low doses of antigen for induction of T cell proliferation. J Immunol. 1985; 135:980–988.
   PubMed Web of Science ®Google Scholar
• Batista FD, Iber D. Neuberger MS: B cells acquire antigen from target cells after synapse formation. Nature. 2011; 411:489–494.
   Google Scholar
• Marino E, Grey ST. A new role for an old player: Do B cells unleash the self-reactive CD8+T cell storm necessary for the development of type 1 diabetes?. J Autoimmun. 2008; 31:301–305.
   PubMed Web of Science ®Google Scholar
• Cox MA, Harrington LE, Zajac AJ. Cytokines and the inception of CD8 T cell responses. Trends Immunol. 2011; 32:180–186.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Wagner DHJr, Vaitaitis G, Sanderson R, Poulin M, Dobbs C, Haskins K. Expression of CD40 identifies a unique pathogenic T cell population in type 1 diabetes. Proc Natl Acad Sci USA. 2002; 99:3782–3787.
   PubMed Web of Science ®Google Scholar
• Ryan GA, Wang CJ, Chamberlain JL, Attridge K, Schmidt EM, Kenefeck R, Clough LE, Dunussi-Joannopoulos K, Toellner KM, Walker LS. B1 cells promote pancreas infiltration by autoreactive T cells. J Immunol. 2010; 185:2800–2807.
   PubMed Web of Science ®Google Scholar
• Xu B, Cook RE, Michie SA. Alpha4beta7 integrin/MAdCAM-1 adhesion pathway is crucial for B cell migration into pancreatic lymph nodes in nonobese diabetic mice. J Autoimmun. 2010; 35:124–129.
   PubMed Web of Science ®Google Scholar
• Kendall PL, Woodward EJ, Hulbert C, Thomas JW. Peritoneal B cells govern the outcome of diabetes in non-obese diabetic mice. Eur J Immunol. 2004; 34:2387–2395.
   PubMed Web of Science ®Google Scholar
• Tian J, Zekzer D, Hanssen L, Lu Y, Olcott A, Kaufman DL. Lipopolysaccharide-activated B cells down-regulate Th1 immunity and prevent autoimmune diabetes in nonobese diabetic mice. J Immunol. 2001; 167:1081–1089.
   PubMed Web of Science ®Google Scholar
• Chervonsky AV, Wang Y, Wong FS, Visintin I, Flavell RA, Janeway CAJr, Matis LA. The role of Fas in autoimmune diabetes. Cell. 1997; 89:17–24.
   PubMed Web of Science ®Google Scholar
• Green EA, Gorelik L, McGregor CM, Tran EH, Flavell RA. CD4+CD25+T regulatory cells control anti-islet CD8+T cells through TGF-beta-TGF-beta receptor interactions in type 1 diabetes. Proc Natl Acad Sci USA. 2003; 100:10878–10883.
   PubMed Web of Science ®Google Scholar
• Hussain S, Delovitch TL. Intravenous transfusion of BCR-activated B cells protects NOD mice from type 1 diabetes in an IL-10-dependent manner. J Immunol. 2007; 179:7225–7232.
   PubMed Web of Science ®Google Scholar
• Mizoguchi A, Mizoguchi E, Smith RN, Preffer FI, Bhan AK. Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice. J Exp Med. 1997; 186:174–156.
   Google Scholar
• Mizoguchi A, Bhan AK. A case for regulatory B cells. J Immunol. 2006; 176:705–710.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Matsushita T, Yanaba K, Bouaziz JD, Fujimoto M, Tedder TF. Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J Clin Invest. 2008; 118:3420–3430.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Noorchashm H, Moore DJ, Lieu YK, Noorchashm N, Schlachterman A, Song HK, Barker CF, Naji A. Contribution of the innate immune system to autoimmune diabetes: a role for the CR1/CR2 complement receptors. Cell Immunol. 1999; 195:75–79.
   PubMed Web of Science ®Google Scholar
• Rolf J, Motta V, Duarte N, Lundholm M, Berntman E, Bergman ML, Sorokin L, Cardell SL, Holmberg D. The enlarged population of marginal zone/CD1d(high) B lymphocytes in nonobese diabetic mice maps to diabetes susceptibility region Idd11. J Immunol. 2005; 174:4821–4827.
   PubMed Web of Science ®Google Scholar
• Quinn WJ3rd, Noorchashm N, Crowley JE, Reed AJ, Noorchashm H, Naji A, Cancro MP. Cutting edge: impaired transitional B cell production and selection in the nonobese diabetic mouse. J Immunol. 2006; 176:7159–7164.
   PubMed Web of Science ®Google Scholar
• Martin F, Kearney JF. Marginal-zone B cells. Nat Rev Immunol. 2002; 2:323–335.
   PubMed Web of Science ®Google Scholar
• Melo ME, Qian J, El-Amine M, Agarwal RK, Soukhareva N, Kang Y, Scott DW. Gene transfer of Ig-fusion proteins into B cells prevents and treats autoimmune diseases. J Immunol. 2002; 168:4788–4795.
   PubMed Web of Science ®Google Scholar
• Su Y, Zhang AH, Li X, Owusu-Boaitey N, Skupsky J, Scott DW. B cells “transduced” with TAT-fusion proteins can induce tolerance and protect mice from diabetes and EAE. Clin Immunol. 2011; 140:260–267.
   Google Scholar
• Lopez MM, Valenzuela JE, Alvarez FC, Lopez-Alvarez MR, Cecilia GS, Paricio PP. Long-term problems related to immunosuppression. Transpl Immunol. 2006; 17:31–35.
   PubMed Web of Science ®Google Scholar
• Wang R, Song L, Han G, Wang J, Chen G, Xu R, Yu M, Qian J, Shen B, Li Y. Mechanisms of regulatory T-cell induction by antigen-IgG-transduced splenocytes. Scand J Immunol. 2007; 66:515–522.
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Groom JR, Fletcher CA, Walters SN, Grey ST, Watt SV, Sweet MJ, Smyth MJ, Mackay CR, Mackay F. BAFF and MyD88 signals promote a lupuslike disease independent of T cells. J Exp Med. 2007; 204:1959–1971.
   PubMed Web of Science ®Google Scholar
• Chen X, Jensen PE. Cutting edge: primary B lymphocytes preferentially expand allogeneic FoxP3+CD4 T cells. J Immunol. 2007; 179:2046–2050.
   PubMedGoogle Scholar
• Zhong X, Gao W, Degauque N, Bai C, Lu Y, Kenny J, Oukka M, Strom TB, Rothstein TL. Reciprocal generation of Th1/Th17 and T(reg) cells by B1 and B2 B cells. Eur J Immunol. 2007; 37:2400–2404.
   PubMed Web of Science ®Google Scholar
• Chen LC, Delgado JC, Jensen PE, Chen X. Direct expansion of human allospecific FoxP3+CD4+regulatory T cells with allogeneic B cells for therapeutic application. J Immunol. 2009; 183:4094–4102.
   PubMed Web of Science ®Google Scholar
• Vinuesa CG, Linterman MA, Goodnow CC, Randall KL. T cells and follicular dendritic cells in germinal center B-cell formation and selection. Immunol Rev. 2010; 237:72–89.
   PubMed Web of Science ®Google Scholar