Non-Antibody-Secreting Functions of B Cells and Their Contribution to Autoimmune Disease

Literature Cited

1. Abdul-Majid KB, Stefferl A, Bourquin C, Lassmann H, Linington C et al. 2002. Fc receptors are critical for autoimmune inflammatory damage to the central nervous system in experimental autoimmune encephalomyelitis. Scand. J. Immunol. 55:70–81
   [Google Scholar]
2. Adlowitz DG, Barnard J, Biear JN, Cistrone C, Owen T et al. 2015. Expansion of activated peripheral blood memory B cells in rheumatoid arthritis, impact of B cell depletion therapy, and biomarkers of response. PLOS ONE 10:e0128269
   [Google Scholar]
3. Aravena O, Ferrier A, Menon M, Mauri C, Aguillon JC et al. 2017. TIM-1 defines a human regulatory B cell population that is altered in frequency and function in systemic sclerosis patients. Arthritis Res. Ther. 19:8
   [Google Scholar]
4. Arkatkar T, Du SW, Jacobs HM, Dam EM, Hou B et al. 2017. B cell–derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity. J. Exp. Med. 214:3207–17
   [Google Scholar]
5. Aschermann S, Lehmann CH, Mihai S, Schett G, Dudziak D, Nimmerjahn F 2013. B cells are critical for autoimmune pathology in Scurfy mice. PNAS 110:19042–47
   [Google Scholar]
6. Attanavanich K, Kearney JF. 2004. Marginal zone, but not follicular B cells, are potent activators of naive CD4 T cells. J. Immunol. 172:803–11
   [Google Scholar]
7. Audia S, Rossato M, Trad M, Samson M, Santegoets K et al. 2017. B cell depleting therapy regulates splenic and circulating T follicular helper cells in immune thrombocytopenia. J. Autoimmun. 77:89–95
   [Google Scholar]
8. Aviszus K, MacLeod MK, Kirchenbaum GA, Detanico TO, Heiser RA et al. 2012. Antigen-specific suppression of humoral immunity by anergic Ars/A1 B cells. J. Immunol. 189:4275–83
   [Google Scholar]
9. Bar-Or A, Fawaz L, Fan B, Darlington PJ, Rieger A et al. 2010. Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS?. Ann. Neurol. 67:452–61
   [Google Scholar]
10. Barr TA, Brown S, Ryan G, Zhao J, Gray D 2007. TLR-mediated stimulation of APC: distinct cytokine responses of B cells and dendritic cells. Eur. J. Immunol. 37:3040–53
    [Google Scholar]
11. Barr TA, Shen P, Brown S, Lampropoulou V, Roch T et al. 2012. B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6-producing B cells. J. Exp. Med. 209:1001–10
    [Google Scholar]
12. Becker-Herman S, Meyer-Bahlburg A, Schwartz MA, Jackson SW, Hudkins KL et al. 2011. WASp-deficient B cells play a critical, cell-intrinsic role in triggering autoimmunity. J. Exp. Med. 208:2033–42
    [Google Scholar]
13. Bermejo DA, Jackson SW, Gorosito-Serran M, Acosta-Rodriguez EV, Amezcua-Vesely MC et al. 2013. Trypanosoma cruzi trans-sialidase initiates a program independent of the transcription factors RORγt and Ahr that leads to IL-17 production by activated B cells. Nat. Immunol. 14:514–22
    [Google Scholar]
14. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB et al. 2006. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–38
    [Google Scholar]
15. Blair PA, Norena LY, Flores-Borja F, Rawlings DJ, Isenberg DA et al. 2010. CD19⁺CD24^hiCD38^hi B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity 32:129–40
    [Google Scholar]
16. Bosma A, Abdel-Gadir A, Isenberg DA, Jury EC, Mauri C 2012. Lipid-antigen presentation by CD1d⁺ B cells is essential for the maintenance of invariant natural killer T cells. Immunity 36:477–90
    [Google Scholar]
17. Bouaziz JD, Yanaba K, Venturi GM, Wang Y, Tisch RM et al. 2007. Therapeutic B cell depletion impairs adaptive and autoreactive CD4⁺ T cell activation in mice. PNAS 104:20878–83
    [Google Scholar]
18. Brink R, Phan TG. 2018. Self-reactive B cells in the germinal center reaction. Annu. Rev. Immunol. 36:339–57
    [Google Scholar]
19. Burnett DL, Langley DB, Schofield P, Hermes JR, Chan TD et al. 2018. Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination. Science 360:223–26
    [Google Scholar]
20. Busconi L, Bauer JW, Tumang JR, Laws A, Perkins-Mesires K et al. 2007. Functional outcome of B cell activation by chromatin immune complex engagement of the B cell receptor and TLR9. J. Immunol. 179:7397–405
    [Google Scholar]
21. Cambridge G, Stohl W, Leandro MJ, Migone TS, Hilbert DM, Edwards JC 2006. Circulating levels of B lymphocyte stimulator in patients with rheumatoid arthritis following rituximab treatment: relationships with B cell depletion, circulating antibodies, and clinical relapse. Arthritis Rheum 54:723–32
    [Google Scholar]
22. Chan O, Shlomchik MJ. 1998. A new role for B cells in systemic autoimmunity: B cells promote spontaneous T cell activation in MRL-lpr/lpr mice. J. Immunol. 160:51–59
    [Google Scholar]
23. Chan OT, Hannum LG, Haberman AM, Madaio MP, Shlomchik MJ 1999. A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus. J. Exp. Med. 189:1639–48
    [Google Scholar]
24. Chaudhry A, Samstein RM, Treuting P, Liang Y, Pils MC et al. 2011. Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation. Immunity 34:566–78
    [Google Scholar]
25. Choi SC, Xu Z, Li W, Yang H, Roopenian DC et al. 2018. Relative contributions of B cells and dendritic cells from lupus-prone mice to CD4⁺ T cell polarization. J. Immunol. 200:3087–99
    [Google Scholar]
26. Colliou N, Picard D, Caillot F, Calbo S, Le Corre S et al. 2013. Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response. Sci. Transl. Med. 5:175ra30
    [Google Scholar]
27. Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y et al. 2007. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450:566–69
    [Google Scholar]
28. Constant S, Schweitzer N, West J, Ranney P, Bottomly K 1995. B lymphocytes can be competent antigen-presenting cells for priming CD4⁺ T cells to protein antigens in vivo. J. Immunol. 155:3734–41
    [Google Scholar]
29. Constant SL. 1999. B lymphocytes as antigen-presenting cells for CD4⁺ T cell priming in vivo. J. Immunol. 162:5695–703
    [Google Scholar]
30. Crawford A, MacLeod M, Schumacher T, Corlett L, Gray D 2006. Primary T cell expansion and differentiation in vivo requires antigen presentation by B cells. J. Immunol. 176:3498–506
    [Google Scholar]
31. Cross AH, Stark JL, Lauber J, Ramsbottom MJ, Lyons JA 2006. Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. J. Neuroimmunol. 180:63–70
    [Google Scholar]
32. de Valle E, Grigoriadis G, O'Reilly LA, Willis SN, Maxwell MJ et al. 2016. NFκB1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells. J. Exp. Med. 213:621–41
    [Google Scholar]
33. Deane KD, O'Donnell CI, Hueber W, Majka DS, Lazar AA et al. 2010. The number of elevated cytokines and chemokines in preclinical seropositive rheumatoid arthritis predicts time to diagnosis in an age-dependent manner. Arthritis Rheum 62:3161–72
    [Google Scholar]
34. Dienz O, Eaton SM, Bond JP, Neveu W, Moquin D et al. 2009. The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4⁺ T cells. J. Exp. Med. 206:69–78
    [Google Scholar]
35. Ding Q, Yeung M, Camirand G, Zeng Q, Akiba H et al. 2011. Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice. J. Clin. Investig. 121:3645–56
    [Google Scholar]
36. Domeier PP, Chodisetti SB, Soni C, Schell SL, Elias MJ et al. 2016. IFN-γ receptor and STAT1 signaling in B cells are central to spontaneous germinal center formation and autoimmunity. J. Exp. Med. 213:715–32
    [Google Scholar]
37. Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P et al. 2004. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med. 350:2572–81
    [Google Scholar]
38. Epstein MM, Di Rosa F, Jankovic D, Sher A, Matzinger P 1995. Successful T cell priming in B cell–deficient mice. J. Exp. Med. 182:915–22
    [Google Scholar]
39. Eris JM, Basten A, Brink R, Doherty K, Kehry MR, Hodgkin PD 1994. Anergic self-reactive B cells present self antigen and respond normally to CD40-dependent T-cell signals but are defective in antigen-receptor-mediated functions. PNAS 91:4392–96
    [Google Scholar]
40. Eynon EE, Parker DC. 1992. Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens. J. Exp. Med. 175:131–38
    [Google Scholar]
41. Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM 2002. B cells regulate autoimmunity by provision of IL-10. Nat. Immunol. 3:944–50
    [Google Scholar]
42. Flach AC, Litke T, Strauss J, Haberl M, Gomez CC et al. 2016. Autoantibody-boosted T-cell reactivation in the target organ triggers manifestation of autoimmune CNS disease. PNAS 113:3323–28
    [Google Scholar]
43. Flores-Borja F, Bosma A, Ng D, Reddy V, Ehrenstein MR et al. 2013. CD19⁺CD24^hiCD38^hi B cells maintain regulatory T cells while limiting T_H1 and T_H17 differentiation. Sci. Transl. Med. 5:173ra23
    [Google Scholar]
44. Fuchs EJ, Matzinger P. 1992. B cells turn off virgin but not memory T cells. Science 258:1156–59
    [Google Scholar]
45. Gavanescu I, Benoist C, Mathis D 2008. B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: a therapeutic approach for APECED patients. PNAS 105:13009–14
    [Google Scholar]
46. Getahun A, Beavers NA, Larson SR, Shlomchik MJ, Cambier JC 2016a. Continuous inhibitory signaling by both SHP-1 and SHIP-1 pathways is required to maintain unresponsiveness of anergic B cells. J. Exp. Med. 213:751–69
    [Google Scholar]
47. Getahun A, Smith MJ, Cambier JC 2016b. Mechanisms of peripheral B cell tolerance. Encyclopedia of Immunobiology MJH Ratcliffe 83–91 Amsterdam: Academic Press
    [Google Scholar]
48. Ghoreschi K, Laurence A, Yang XP, Tato CM, McGeachy MJ et al. 2010. Generation of pathogenic T_H17 cells in the absence of TGF-β signalling. Nature 467:967–71
    [Google Scholar]
49. Giles JR, Kashgarian M, Koni PA, Shlomchik MJ 2015. B cell–specific MHC class II deletion reveals multiple nonredundant roles for B cell antigen presentation in murine lupus. J. Immunol. 195:2571–79
    [Google Scholar]
50. Green NM, Laws A, Kiefer K, Busconi L, Kim YM et al. 2009. Murine B cell response to TLR7 ligands depends on an IFN-β feedback loop. J. Immunol. 183:1569–76
    [Google Scholar]
51. Green NM, Moody KS, Debatis M, Marshak-Rothstein A 2012. Activation of autoreactive B cells by endogenous TLR7 and TLR3 RNA ligands. J. Biol. Chem. 287:39789–99
    [Google Scholar]
52. Griffin DO, Rothstein TL. 2011. A small CD11b⁺ human B1 cell subpopulation stimulates T cells and is expanded in lupus. J. Exp. Med. 208:2591–98
    [Google Scholar]
53. Guilliams M, Bruhns P, Saeys Y, Hammad H, Lambrecht BN 2014. The function of Fcγ receptors in dendritic cells and macrophages. Nat. Rev. Immunol. 14:94–108
    [Google Scholar]
54. Haas KM, Watanabe R, Matsushita T, Nakashima H, Ishiura N et al. 2010. Protective and pathogenic roles for B cells during systemic autoimmunity in NZB/W F1 mice. J. Immunol. 184:4789–800
    [Google Scholar]
55. Hardy IR, Anceriz N, Rousseau F, Seefeldt MB, Hatterer E et al. 2014. Anti-CD79 antibody induces B cell anergy that protects against autoimmunity. J. Immunol. 192:1641–50
    [Google Scholar]
56. Harris DP, Goodrich S, Gerth AJ, Peng SL, Lund FE 2005a. Regulation of IFN-γ production by B effector 1 cells: essential roles for T-bet and the IFN-γ receptor. J. Immunol. 174:6781–90
    [Google Scholar]
57. Harris DP, Goodrich S, Mohrs K, Mohrs M, Lund FE 2005b. The development of IL-4-producing B cells (B effector 2 cells) is controlled by IL-4, IL-4 receptor α, and Th2 cells. J. Immunol. 175:7103–7
    [Google Scholar]
58. Harris DP, Haynes L, Sayles PC, Duso DK, Eaton SM et al. 2000. Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat. Immunol. 1:475–82
    [Google Scholar]
59. Hartwell BL, Pickens CJ, Leon M, Northrup L, Christopher MA et al. 2018. Soluble antigen arrays disarm antigen-specific B cells to promote lasting immune tolerance in experimental autoimmune encephalomyelitis. J. Autoimmun. 93:76–88
    [Google Scholar]
60. Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J et al. 2008. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N. Engl. J. Med. 358:676–88
    [Google Scholar]
61. Heink S, Yogev N, Garbers C, Herwerth M, Aly L et al. 2017. Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic TH17 cells. Nat. Immunol. 18:74–85
    [Google Scholar]
62. Ho WY, Cooke MP, Goodnow CC, Davis MM 1994. Resting and anergic B cells are defective in CD28-dependent costimulation of naive CD4⁺ T cells. J. Exp. Med. 179:1539–49
    [Google Scholar]
63. Hsu P, Santner-Nanan B, Hu M, Skarratt K, Lee CH et al. 2015. IL-10 potentiates differentiation of human induced regulatory T cells via STAT3 and Foxo1. J. Immunol. 195:3665–74
    [Google Scholar]
64. Hulbert C, Riseili B, Rojas M, Thomas JW 2001. B cell specificity contributes to the outcome of diabetes in nonobese diabetic mice. J. Immunol. 167:5535–38
    [Google Scholar]
65. Inoue Y, Kaifu T, Sugahara-Tobinai A, Nakamura A, Miyazaki J, Takai T 2007. Activating Fcγ receptors participate in the development of autoimmune diabetes in NOD mice. J. Immunol. 179:764–74
    [Google Scholar]
66. Iwata Y, Matsushita T, Horikawa M, Dilillo DJ, Yanaba K et al. 2011. Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 117:530–41
    [Google Scholar]
67. Jackson SW, Jacobs HM, Arkatkar T, Dam EM, Scharping NE et al. 2016. B cell IFN-γ receptor signaling promotes autoimmune germinal centers via cell-intrinsic induction of BCL-6. J. Exp. Med. 213:733–50
    [Google Scholar]
68. Jain S, Park G, Sproule TJ, Christianson GJ, Leeth CM et al. 2016. Interleukin 6 accelerates mortality by promoting the progression of the systemic lupus erythematosus–like disease of BXSB.Yaa mice. PLOS ONE 11:e0153059
    [Google Scholar]
69. Jelcic I, Al Nimer F, Wang J, Lentsch V, Planas R et al. 2018. Memory B cells activate brain-homing, autoreactive CD4⁺ T cells in multiple sclerosis. Cell 175:85–100 e23
    [Google Scholar]
70. Kalampokis I, Venturi GM, Poe JC, Dvergsten JA, Sleasman JW, Tedder TF 2017. The regulatory B cell compartment expands transiently during childhood and is contracted in children with autoimmunity. Arthritis Rheumatol 69:225–38
    [Google Scholar]
71. Kendall PL, Case JB, Sullivan AM, Holderness JS, Wells KS et al. 2013. Tolerant anti-insulin B cells are effective APCs. J. Immunol. 190:2519–26
    [Google Scholar]
72. Khan AR, Hams E, Floudas A, Sparwasser T, Weaver CT, Fallon PG 2015. PD-L1^hi B cells are critical regulators of humoral immunity. Nat. Commun. 6:5997
    [Google Scholar]
73. Kleffel S, Vergani A, Tezza S, Ben Nasr M, Niewczas MA et al. 2015. Interleukin-10⁺ regulatory B cells arise within antigen-experienced CD40⁺ B cells to maintain tolerance to islet autoantigens. Diabetes 64:158–71
    [Google Scholar]
74. Lassila O, Vainio O, Matzinger P 1988. Can B cells turn on virgin T cells. Nature 334:253–55
    [Google Scholar]
75. Leadbetter EA, Rifkin IR, Hohlbaum AM, Beaudette BC, Shlomchik MJ, Marshak-Rothstein A 2002. Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature 416:603–7
    [Google Scholar]
76. Leeth CM, Racine J, Chapman HD, Arpa B, Carrillo J et al. 2016. B-lymphocytes expressing an immunoglobulin specificity recognizing the pancreatic β-cell autoantigen peripherin are potent contributors to type 1 diabetes development in NOD mice. Diabetes 65:1977–87
    [Google Scholar]
77. Leonardo SM, De Santis JL, Gehrand A, Malherbe LP, Gauld SB 2012. Expansion of follicular helper T cells in the absence of Treg cells: implications for loss of B-cell anergy. Eur. J. Immunol. 42:2597–607
    [Google Scholar]
78. Li R, Rezk A, Miyazaki Y, Hilgenberg E, Touil H et al. 2015. Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy. Sci. Transl. Med. 7:310ra166
    [Google Scholar]
79. Liu Z, Dang E, Li B, Qiao H, Jin L et al. 2018. Dysfunction of CD19⁺CD24^hiCD27⁺ B regulatory cells in patients with bullous pemphigoid. Sci. Rep. 8:703
    [Google Scholar]
80. Looney RJ, Anolik JH, Campbell D, Felgar RE, Young F et al. 2004. B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum 50:2580–89
    [Google Scholar]
81. Lu R, Munroe ME, Guthridge JM, Bean KM, Fife DA et al. 2016. Dysregulation of innate and adaptive serum mediators precedes systemic lupus erythematosus classification and improves prognostic accuracy of autoantibodies. J. Autoimmun. 74:182–93
    [Google Scholar]
82. Ludwig RJ, Vanhoorelbeke K, Leypoldt F, Kaya Z, Bieber K et al. 2017. Mechanisms of autoantibody-induced pathology. Front. Immunol. 8:603
    [Google Scholar]
83. Lund FE, Randall TD. 2010. Effector and regulatory B cells: modulators of CD4⁺ T cell immunity. Nat. Rev. Immunol. 10:236–47
    [Google Scholar]
84. Lyons JA, San M, Happ MP, Cross AH 1999. B cells are critical to induction of experimental allergic encephalomyelitis by protein but not by a short encephalitogenic peptide. Eur. J. Immunol. 29:3432–39
    [Google Scholar]
85. Mannoor K, Xu Y, Chen C 2013. Natural autoantibodies and associated B cells in immunity and autoimmunity. Autoimmunity 46:138–47
    [Google Scholar]
86. Marino E, Tan B, Binge L, Mackay CR, Grey ST 2012. B-cell cross-presentation of autologous antigen precipitates diabetes. Diabetes 61:2893–905
    [Google Scholar]
87. Matsumoto M, Baba A, Yokota T, Nishikawa H, Ohkawa Y et al. 2014. Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation. Immunity 41:1040–51
    [Google Scholar]
88. Matsushita T, Horikawa M, Iwata Y, Tedder TF 2010. Regulatory B cells (B10 cells) and regulatory T cells have independent roles in controlling experimental autoimmune encephalomyelitis initiation and late-phase immunopathogenesis. J. Immunol. 185:2240–52
    [Google Scholar]
89. Matsushita T, Kobayashi T, Mizumaki K, Kano M, Sawada T et al. 2018. BAFF inhibition attenuates fibrosis in scleroderma by modulating the regulatory and effector B cell balance. Sci. Adv. 4:eaas9944
    [Google Scholar]
90. Matsushita T, Yanaba K, Bouaziz JD, Fujimoto M, Tedder TF 2008. Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J. Clin. Investig. 118:3420–30
    [Google Scholar]
91. Mauri C, Gray D, Mushtaq N, Londei M 2003. Prevention of arthritis by interleukin 10-producing B cells. J. Exp. Med. 197:489–501
    [Google Scholar]
92. Mauri C, Menon M. 2017. Human regulatory B cells in health and disease: therapeutic potential. J. Clin. Investig. 127:772–79
    [Google Scholar]
93. Menard LC, Minns LA, Darche S, Mielcarz DW, Foureau DM et al. 2007. B cells amplify IFN-γ production by T cells via a TNF-α-mediated mechanism. J. Immunol. 179:4857–66
    [Google Scholar]
94. Menon M, Blair PA, Isenberg DA, Mauri C 2016. A regulatory feedback between plasmacytoid dendritic cells and regulatory B cells is aberrant in systemic lupus erythematosus. Immunity 44:683–97
    [Google Scholar]
95. Merrell KT, Benschop RJ, Gauld SB, Aviszus K, Decote-Ricardo D et al. 2006. Identification of anergic B cells within a wild-type repertoire. Immunity 25:953–62
    [Google Scholar]
96. Molnarfi N, Schulze-Topphoff U, Weber MS, Patarroyo JC, Prod'homme T et al. 2013. MHC class II–dependent B cell APC function is required for induction of CNS autoimmunity independent of myelin-specific antibodies. J. Exp. Med. 210:2921–37
    [Google Scholar]
97. Monroe JG, Cambier JC. 1983. B cell activation. III. B cell plasma membrane depolarization and hyper-Ia antigen expression induced by receptor immunoglobulin cross-linking are coupled. J. Exp. Med. 158:1589–99
    [Google Scholar]
98. Monson NL, Cravens P, Hussain R, Harp CT, Cummings M et al. 2011. Rituximab therapy reduces organ-specific T cell responses and ameliorates experimental autoimmune encephalomyelitis. PLOS ONE 6:e17103
    [Google Scholar]
99. Morlacchi S, Soldani C, Viola A, Sarukhan A 2011. Self-antigen presentation by mouse B cells results in regulatory T-cell induction rather than anergy or clonal deletion. Blood 118:984–91
    [Google Scholar]
100. Morris SC, Lees A, Finkelman FD 1994a. In vivo activation of naive T cells by antigen-presenting B cells. J. Immunol. 152:3777–85
     [Google Scholar]
101. Morris SC, Lees A, Holmes JM, Jeffries RD, Finkelman FD 1994b. Induction of B cell and T cell tolerance in vivo by anti-CD23 mAb. J. Immunol. 152:3768–76
     [Google Scholar]
102. Murray SE, Toren KG, Parker DC 2013. Peripheral CD4⁺ T-cell tolerance is induced in vivo by rare antigen-bearing B cells in follicular, marginal zone, and B-1 subsets. Eur. J. Immunol. 43:1818–27
     [Google Scholar]
103. Nagafuchi H, Suzuki N, Mizushima Y, Sakane T 1993. Constitutive expression of IL-6 receptors and their role in the excessive B cell function in patients with systemic lupus erythematosus. J. Immunol. 151:6525–34
     [Google Scholar]
104. Nemazee D. 2017. Mechanisms of central tolerance for B cells. Nat. Rev. Immunol. 17:281–94
     [Google Scholar]
105. Nielsen CH, Bornsen L, Sellebjerg F, Brimnes MK 2016. Myelin basic protein–induced production of tumor necrosis factor-α and interleukin-6, and presentation of the immunodominant peptide MBP85-99 by B cells from patients with relapsing-remitting multiple sclerosis. PLOS ONE 11:e0146971
     [Google Scholar]
106. Noorchashm H, Lieu YK, Noorchashm N, Rostami SY, Greeley SA et al. 1999. 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. 163:743–50
     [Google Scholar]
107. Nurieva RI, Chung Y, Martinez GJ, Yang XO, Tanaka S et al. 2009. Bcl6 mediates the development of T follicular helper cells. Science 325:1001–5
     [Google Scholar]
108. Olalekan SA, Cao Y, Hamel KM, Finnegan A 2015. B cells expressing IFN-γ suppress Treg-cell differentiation and promote autoimmune experimental arthritis. Eur. J. Immunol. 45:988–98
     [Google Scholar]
109. Oleinika K, Rosser EC, Matei DE, Nistala K, Bosma A et al. 2018. CD1d-dependent immune suppression mediated by regulatory B cells through modulations of iNKT cells. Nat. Commun. 9:684
     [Google Scholar]
110. Parker Harp CR, Archambault AS, Sim J, Ferris ST, Mikesell RJ et al. 2015. B cell antigen presentation is sufficient to drive neuroinflammation in an animal model of multiple sclerosis. J. Immunol. 194:5077–84
     [Google Scholar]
111. Parker Harp CR, Archambault AS, Sim J, Shlomchik MJ, Russell JH, Wu GF 2018. B cells are capable of independently eliciting rapid reactivation of encephalitogenic CD4 T cells in a murine model of multiple sclerosis. PLOS ONE 13:e0199694
     [Google Scholar]
112. Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Becker DJ, Gitelman SE et al. 2009. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N. Engl. J. Med. 361:2143–52
     [Google Scholar]
113. Piccio L, Naismith RT, Trinkaus K, Klein RS, Parks BJ et al. 2010. Changes in B- and T-lymphocyte and chemokine levels with rituximab treatment in multiple sclerosis. Arch. Neurol. 67:707–14
     [Google Scholar]
114. Pierson ER, Stromnes IM, Goverman JM 2014. B cells promote induction of experimental autoimmune encephalomyelitis by facilitating reactivation of T cells in the central nervous system. J. Immunol. 192:929–39
     [Google Scholar]
115. Rathmell JC, Fournier S, Weintraub BC, Allison JP, Goodnow CC 1998. Repression of B7.2 on self-reactive B cells is essential to prevent proliferation and allow Fas-mediated deletion by CD4⁺ T cells. J. Exp. Med. 188:651–59
     [Google Scholar]
116. Rock KL, Benacerraf B, Abbas AK 1984. Antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors. J. Exp. Med. 160:1102–13
     [Google Scholar]
117. Ronchese F, Hausmann B. 1993. B lymphocytes in vivo fail to prime naive T cells but can stimulate antigen-experienced T lymphocytes. J. Exp. Med. 177:679–90
     [Google Scholar]
118. Rubtsov AV, Rubtsova K, Kappler JW, Jacobelli J, Friedman RS, Marrack P 2015. CD11c-expressing B cells are located at the T cell/B cell border in spleen and are potent APCs. J. Immunol. 195:71–79
     [Google Scholar]
119. Rubtsova K, Rubtsov AV, Thurman JM, Mennona JM, Kappler JW, Marrack P 2017. B cells expressing the transcription factor T-bet drive lupus-like autoimmunity. J. Clin. Investig. 127:1392–404
     [Google Scholar]
120. Sabouri Z, Schofield P, Horikawa K, Spierings E, Kipling D et al. 2014. Redemption of autoantibodies on anergic B cells by variable-region glycosylation and mutation away from self-reactivity. PNAS 111:E2567–75
     [Google Scholar]
121. Sentis A, Diekmann F, Llobell A, de Moner N, Espinosa G et al. 2017. Kinetic analysis of changes in T- and B-lymphocytes after anti-CD20 treatment in renal pathology. Immunobiology 222:620–30
     [Google Scholar]
122. Seo SJ, Fields ML, Buckler JL, Reed AJ, Mandik-Nayak L et al. 2002. The impact of T helper and T regulatory cells on the regulation of anti-double-stranded DNA B cells. Immunity 16:535–46
     [Google Scholar]
123. Serreze DV, Chapman HD, Varnum DS, Hanson MS, Reifsnyder PC et al. 1996. 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. 184:2049–53
     [Google Scholar]
124. Serreze DV, Fleming SA, Chapman HD, Richard SD, Leiter EH, Tisch RM 1998. B lymphocytes are critical antigen-presenting cells for the initiation of T cell–mediated autoimmune diabetes in nonobese diabetic mice. J. Immunol. 161:3912–18
     [Google Scholar]
125. Shen P, Roch T, Lampropoulou V, O'Connor RA, Stervbo U et al. 2014. IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature 507:366–70
     [Google Scholar]
126. Shlomchik MJ, Madaio MP, Ni D, Trounstein M, Huszar D 1994. The role of B cells in lpr/lpr-induced autoimmunity. J. Exp. Med. 180:1295–306
     [Google Scholar]
127. Silva DG, Daley SR, Hogan J, Lee SK, Teh CE et al. 2011. Anti-islet autoantibodies trigger autoimmune diabetes in the presence of an increased frequency of islet-reactive CD4 T cells. Diabetes 60:2102–11
     [Google Scholar]
128. Silveira PA, Johnson E, Chapman HD, Bui T, Tisch RM, Serreze DV 2002. The preferential ability of B lymphocytes to act as diabetogenic APC in NOD mice depends on expression of self-antigen-specific immunoglobulin receptors. Eur. J. Immunol. 32:3657–66
     [Google Scholar]
129. Smith MJ, Hinman RM, Getahun A, Kim S, Packard TA, Cambier JC 2018. Silencing of high-affinity insulin-reactive B lymphocytes by anergy and impact of the NOD genetic background in mice. Diabetologia 61:2621–32
     [Google Scholar]
130. Stasi R, Del Poeta G, Stipa E, Evangelista ML, Trawinska MM et al. 2007. Response to B-cell depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura. Blood 110:2924–30
     [Google Scholar]
131. Svensson L, Abdul-Majid KB, Bauer J, Lassmann H, Harris RA, Holmdahl R 2002. A comparative analysis of B cell–mediated myelin oligodendrocyte glycoprotein–experimental autoimmune encephalomyelitis pathogenesis in B cell–deficient mice reveals an effect on demyelination. Eur. J. Immunol. 32:1939–46
     [Google Scholar]
132. Takemura S, Klimiuk PA, Braun A, Goronzy JJ, Weyand CM 2001. T cell activation in rheumatoid synovium is B cell dependent. J. Immunol. 167:4710–18
     [Google Scholar]
133. Tamimoto Y, Horiuchi T, Tsukamoto H, Otsuka J, Mitoma H et al. 2008. A dose-escalation study of rituximab for treatment of systemic lupus erythematosus and Evans' syndrome: immunological analysis of B cells, T cells and cytokines. Rheumatology 47:821–27
     [Google Scholar]
134. Teague BN, Pan Y, Mudd PA, Nakken B, Zhang Q et al. 2007. Transitional T3 B cells do not give rise to mature B cells, have undergone selection, and are reduced in murine lupus. J. Immunol. 178:7511–15
     [Google Scholar]
135. Teichmann LL, Ols ML, Kashgarian M, Reizis B, Kaplan DH, Shlomchik MJ 2010. Dendritic cells in lupus are not required for activation of T and B cells but promote their expansion, resulting in tissue damage. Immunity 33:967–78
     [Google Scholar]
136. Townsend SE, Goodnow CC. 1998. Abortive proliferation of rare T cells induced by direct or indirect antigen presentation by rare B cells in vivo. J. Exp. Med. 187:1611–21
     [Google Scholar]
137. Tsantikos E, Oracki SA, Quilici C, Anderson GP, Tarlinton DM, Hibbs ML 2010. Autoimmune disease in Lyn-deficient mice is dependent on an inflammatory environment established by IL-6. J. Immunol. 184:1348–60
     [Google Scholar]
138. van de Veerdonk FL, Lauwerys B, Marijnissen RJ, Timmermans K, Di Padova F et al. 2011. The anti-CD20 antibody rituximab reduces the Th17 cell response. Arthritis Rheum 63:1507–16
     [Google Scholar]
139. Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B 2006. TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24:179–89
     [Google Scholar]
140. Wan X, Thomas JW, Unanue ER 2016. Class-switched anti-insulin antibodies originate from unconventional antigen presentation in multiple lymphoid sites. J. Exp. Med. 213:967–78
     [Google Scholar]
141. Wang RX, Yu CR, Dambuza IM, Mahdi RM, Dolinska MB et al. 2014. Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat. Med. 20:633–41
     [Google Scholar]
142. Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E, Nussenzweig MC 2003. Predominant autoantibody production by early human B cell precursors. Science 301:1374–77
     [Google Scholar]
143. Watanabe R, Ishiura N, Nakashima H, Kuwano Y, Okochi H et al. 2010. Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity. J. Immunol. 184:4801–9
     [Google Scholar]
144. Wolf SD, Dittel BN, Hardardottir F, Janeway CA Jr. 1996. Experimental autoimmune encephalomyelitis induction in genetically B cell–deficient mice. J. Exp. Med. 184:2271–78
     [Google Scholar]
145. Xiao S, Brooks CR, Sobel RA, Kuchroo VK 2015. Tim-1 is essential for induction and maintenance of IL-10 in regulatory B cells and their regulation of tissue inflammation. J. Immunol. 194:1602–8
     [Google Scholar]
146. Xiu Y, Wong CP, Bouaziz JD, Hamaguchi Y, Wang Y et al. 2008. B lymphocyte depletion by CD20 monoclonal antibody prevents diabetes in nonobese diabetic mice despite isotype-specific differences in FcγR effector functions. J. Immunol. 180:2863–75
     [Google Scholar]
147. Xu X, Shi Y, Cai Y, Zhang Q, Yang F et al. 2013. Inhibition of increased circulating Tfh cell by anti-CD20 monoclonal antibody in patients with type 1 diabetes. PLOS ONE 8:e79858
     [Google Scholar]
148. Yanaba K, Bouaziz JD, Haas KM, Poe JC, Fujimoto M, Tedder TF 2008. A regulatory B cell subset with a unique CD1d^hiCD5⁺ phenotype controls T cell–dependent inflammatory responses. Immunity 28:639–50
     [Google Scholar]
149. Yanaba K, Bouaziz JD, Matsushita T, Tsubata T, Tedder TF 2009. The development and function of regulatory B cells expressing IL-10 (B10 cells) requires antigen receptor diversity and TLR signals. J. Immunol. 182:7459–72
     [Google Scholar]
150. Yoshizaki A, Miyagaki T, DiLillo DJ, Matsushita T, Horikawa M et al. 2012. Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature 491:264–68
     [Google Scholar]
151. Zhang AH, Yoon J, Kim YC, Scott DW 2018. Targeting antigen-specific B cells using antigen-expressing transduced regulatory T cells. J. Immunol. 201:1434–41
     [Google Scholar]
152. Zhang R, Sage PT, Finn K, Huynh A, Blazar BR et al. 2017. B cells drive autoimmunity in mice with CD28-deficient regulatory T cells. J. Immunol. 199:3972–80
     [Google Scholar]
153. Zhao C, Li HZ, Zhao DD, Ma C, Wu F et al. 2017. Increased circulating T follicular helper cells are inhibited by rituximab in neuromyelitis optica spectrum disorder. Front. Neurol. 8:104
     [Google Scholar]
154. Zhao Y, Lutalo PM, Thomas JE, Sangle S, Choong LM et al. 2014. Circulating T follicular helper cell and regulatory T cell frequencies are influenced by B cell depletion in patients with granulomatosis with polyangiitis. Rheumatology 53:621–30
     [Google Scholar]
155. Zhong X, Gao W, Degauque N, Bai C, Lu Y et al. 2007. Reciprocal generation of Th1/Th17 and T_reg cells by B1 and B2 B cells. Eur. J. Immunol. 37:2400–4
     [Google Scholar]