The expanding family of regulatory B cells

Abstract

Over the last decade it has become evident that in addition to producing antibody, B cells activate the immune system by producing cytokines and via antigen presentation. In addition, B cells also exhibit immunosuppressive functions via diverse regulatory mechanisms. This subset of B cells, known as regulatory B cells (Bregs), contributes to the maintenance of tolerance, primarily via the production of IL-10. Studies in experimental animal models, as well as in patients with autoimmune diseases, have identified multiple Breg subsets exhibiting diverse mechanisms of immune suppression. In this review, we describe the different Breg subsets identified in mice and humans, and their diverse mechanisms of suppression in different disease settings.

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References 68

1. 1.

   Mauri C. and Bosma A. 2012. Immune regulatory function of B cells. Annu. Rev. Immunol. 30:221.

   Not in our library10.1146/annurev-immunol-020711-074934

2. 2.

   Wolf S. D. Dittel B. N. Hardardottir F. and Janeway C. A. Jr. 1996. Experimental autoimmune encephalomyelitis induction in genetically B cell-deficient mice. J. Exp. Med. 184:2271.

   Not in our library10.1084/jem.184.6.2271

3. 3.

   Fillatreau S. Sweenie C. H. McGeachy M. J. Gray D. and Anderton S. M. 2002. B cells regulate autoimmunity by provision of IL-10. Nat. Immunol. 3:944.

   Not in our library10.1038/ni833

4. 4.

   Mizoguchi A. Mizoguchi E. Takedatsu H. Blumberg R. S. and Bhan A. K. 2002. Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity 16:219.

   Not in our library10.1016/s1074-7613(02)00274-1

5. 5.

   Mauri C. Gray D. Mushtaq N. and Londei M. 2003. Prevention of arthritis by interleukin 10-producing B cells. J. Exp. Med. 197:489.

   Not in our library10.1084/jem.20021293

6. 6.
   Interleukin-10 produced by B cells is crucial for the suppression of Th17/Th1 responses, induction of T regulatory type 1 cells and reduction of collagen-induced arthritis · 2012

   No notice
7. 7.

   Evans J. G. Chavez-Rueda K. A. Eddaoudi A.. 2007. Novel suppressive function of transitional 2 B cells in experimental arthritis. J. Immunol. 178:7868.

   Not in our library10.4049/jimmunol.178.12.7868

8. 8.

   Gray M. Miles K. Salter D. Gray D. and Savill J. 2007. Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory B cells. Proc. Natl Acad. Sci. USA 104:14080.

   Not in our library10.1073/pnas.0700326104

9. 9.

   Yanaba K. Bouaziz J. D. Haas K. M. Poe J. C. Fujimoto M. and Tedder T. F. 2008. A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity 28:639.

   Not in our library10.1016/j.immuni.2008.03.017

10. 10.

    O’Garra A. Chang R. Go N. Hastings R. Haughton G. and Howard M. 1992. Ly-1 B (B-1) cells are the main source of B cell-derived interleukin 10. Eur. J. Immunol. 22:711.

    Not in our library10.1002/eji.1830220314

11. 11.

    Lundy S. K. and Fox D. A. 2009. Reduced Fas ligand-expressing splenic CD5+ B lymphocytes in severe collagen-induced arthritis. Arthritis Res. Ther. 11:R128.

    Not in our library10.1186/ar2795

12. 12.

    Rafei M. Hsieh J. Zehntner S.. 2009. A granulocyte-macrophage colony-stimulating factor and interleukin-15 fusokine induces a regulatory B cell population with immune suppressive properties. Nat. Med. 15:1038.

    Not in our library10.1038/nm.2003

13. 13.

    Shen P. Roch T. Lampropoulou V.. 2014. IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature 507:366.

    Not in our library10.1038/nature12979

14. 14.

    Matsumoto M. Baba A. Yokota T.. 2014. Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation. Immunity 41:1040.

    Not in our library10.1016/j.immuni.2014.10.016

15. 15.

    Ding Q. Yeung M. Camirand G.. 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. Invest. 121:3645.

    Not in our library10.1172/jci46274

16. 16.

    Khan A. R. Hams E. Floudas A. Sparwasser T. Weaver C. T. and Fallon P. G. 2015. PD-L1hi B cells are critical regulators of humoral immunity. Nat. Commun. 6:5997.

    Not in our library10.1038/ncomms6997

17. 17.

    Kaku H. Cheng K. F. Al-Abed Y. and Rothstein T. L. 2014. A novel mechanism of B cell-mediated immune suppression through CD73 expression and adenosine production. J. Immunol. 193:5904.

    Not in our library10.4049/jimmunol.1400336

18. 18.

    Blair P. A. Chavez-Rueda K. A. Evans J. G.. 2009. 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. 182:3492.

    Not in our library10.4049/jimmunol.0803052

19. 19.

    Schioppa T. Moore R. Thompson R. G.. 2011. B regulatory cells and the tumor-promoting actions of TNF-α during squamous carcinogenesis. Proc. Natl Acad. Sci. USA 108:10662.

    Not in our library10.1073/pnas.1100994108

20. 20.

    Amu S. Saunders S. P. Kronenberg M. Mangan N. E. Atzberger A. and Fallon P. G. 2010. Regulatory B cells prevent and reverse allergic airway inflammation via FoxP3-positive T regulatory cells in a murine model. J. Allergy Clin. Immunol. 125:1114.

    Not in our library10.1016/j.jaci.2010.01.018

21. 21.

    Carter N. A. Vasconcellos R. Rosser E. C.. 2011. Mice lacking endogenous IL-10-producing regulatory B cells develop exacerbated disease and present with an increased frequency of Th1/Th17 but a decrease in regulatory T cells. J. Immunol. 186:5569.

    Not in our library10.4049/jimmunol.1100284

22. 22.

    Sayi A. Kohler E. Toller I. M.. 2011. TLR-2-activated B cells suppress Helicobacter-induced preneoplastic gastric immunopathology by inducing T regulatory-1 cells. J. Immunol. 186:878.

    Not in our library10.4049/jimmunol.1002269

23. 23.

    Moreau A. Blair P. A. Chai J. G.. 2015. Transitional-2 B cells acquire regulatory function during tolerance induction and contribute to allograft survival. Eur. J. Immunol. 45:843.

    Not in our library10.1002/eji.201445082

24. 24.

    Srivastava B. Lindsley R. C. Nikbakht N. and Allman D. 2005. Models for peripheral B cell development and homeostasis. Semin. Immunol. 17:175.

    Not in our library10.1016/j.smim.2005.02.008

25. 25.

    Bankoti R. Gupta K. Levchenko A. and Stäger S. 2012. Marginal zone B cells regulate antigen-specific T cell responses during infection. J. Immunol. 188:3961.

    Not in our library10.4049/jimmunol.1102880

26. 26.

    Yanaba K. Bouaziz J. D. Matsushita T. Tsubata T. and Tedder T. F. 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.

    Not in our library10.4049/jimmunol.0900270

27. 27.

    Matsushita T. Yanaba K. Bouaziz J. D. Fujimoto M. and Tedder T. F. 2008. Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J. Clin. Invest. 118:3420.

    Not in our library10.1172/jci36030

28. 28.

    Yang M. Deng J. Liu Y.. 2012. IL-10-producing regulatory B10 cells ameliorate collagen-induced arthritis via suppressing Th17 cell generation. Am. J. Pathol. 180:2375.

    Not in our library10.1016/j.ajpath.2012.03.010

29. 29.

    Watanabe R. Ishiura N. Nakashima H.. 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.

    Not in our library10.4049/jimmunol.0902385

30. 30.

    Yanaba K. Yoshizaki A. Asano Y. Kadono T. Tedder T. F. and Sato S. 2011. IL-10-producing regulatory B10 cells inhibit intestinal injury in a mouse model. Am. J. Pathol. 178:735.

    Not in our library10.1016/j.ajpath.2010.10.022

31. 31.

    Yoshizaki A. Miyagaki T. DiLillo D. J.. 2012. Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature 491:264.

    Not in our library10.1038/nature11501

32. 32.
    IL-10-producing regulatory B cells (B10 cells) in autoimmune disease · 2013

    No notice
33. 33.

    Maseda D. Smith S. H. DiLillo D. J.. 2012. Regulatory B10 cells differentiate into antibody-secreting cells after transient IL-10 production in vivo. J. Immunol. 188:1036.

    Not in our library10.4049/jimmunol.1102500

34. 34.

    Niedbala W. Wei X. Q. Cai B.. 2007. IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur. J. Immunol. 37:3021.

    Not in our library10.1002/eji.200737810

35. 35.

    Collison L. W. Workman C. J. Kuo T. T.. 2007. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450:566.

    Not in our library10.1038/nature06306

36. 36.

    Wang R. X. Yu C. R. Dambuza I. M.. 2014. Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat. Med. 20:633.

    Not in our library10.1038/nm.3554

37. 37.

    Kuchroo V. K. Dardalhon V. Xiao S. and Anderson A. C. 2008. New roles for TIM family members in immune regulation. Nat. Rev. Immunol. 8:577.

    Not in our library10.1038/nri2366

38. 38.

    Shalapour S. Font-Burgada J. Di Caro G.. 2015. Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy. Nature 521:94.

    Not in our library10.1038/nature14395

39. 39.

    Liu J. Zhan W. Kim C. J.. 2014. IL-10-producing B cells are induced early in HIV-1 infection and suppress HIV-1-specific T cell responses. PLoS One 9:e89236.

    Not in our library10.1371/journal.pone.0089236

40. 40.

    Shi B. Y. Xiao L. Gao Y.. 2011. [Identification and functional study of Tim-1(+)CD19(+) regulatory B cell in kidney transplantation recipients]. Zhonghua Yi Xue Za Zhi 91:3388.

    Not in our library

41. 41.

    Xiao S. Brooks C. R. Zhu C.. 2012. Defect in regulatory B-cell function and development of systemic autoimmunity in T-cell Ig mucin 1 (Tim-1) mucin domain-mutant mice. Proc. Natl Acad. Sci. USA 109:12105.

    Not in our library10.1073/pnas.1120914109

42. 42.

    Xiao S. Brooks C. R. Sobel R. A. and Kuchroo V. K. 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.

    Not in our library10.4049/jimmunol.1402632

43. 43.

    Yeung M. Y. Ding Q. Brooks C. R.. 2015. TIM-1 signaling is required for maintenance and induction of regulatory B cells. Am. J. Transplant. 15:942.

    Not in our library10.1111/ajt.13087

44. 44.

    Hardy R. R. 2006. B-1 B cell development. J. Immunol. 177:2749.

    Not in our library10.4049/jimmunol.177.5.2749

45. 45.

    Zhang X. Deriaud E. Jiao X. Braun D. Leclerc C. and Lo-Man R. 2007. Type I interferons protect neonates from acute inflammation through interleukin 10-producing B cells. J. Exp. Med. 204:1107.

    Not in our library10.1084/jem.20062013

46. 46.

    Lundy S. K. and Boros D. L. 2002. Fas ligand-expressing B-1a lymphocytes mediate CD4(+)-T-cell apoptosis during schistosomal infection: induction by interleukin 4 (IL-4) and IL-10. Infect. Immun. 70:812.

    Not in our library10.1128/iai.70.2.812-819.2002

47. 47.

    Shimomura Y. Mizoguchi E. Sugimoto K.. 2008. Regulatory role of B-1 B cells in chronic colitis. Int. Immunol. 20:729.

    Not in our library10.1093/intimm/dxn031

48. 48.

    Deaglio S. Dwyer K. M. Gao W.. 2007. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J. Exp. Med. 204:1257.

    Not in our library10.1084/jem.20062512

49. 49.

    Correale J. Farez M. and Razzitte G. 2008. Helminth infections associated with multiple sclerosis induce regulatory B cells. Ann. Neurol. 64:187.

    Not in our library10.1002/ana.21438

50. 50.

    Blair P. A. Noreña L. Y. Flores-Borja F.. 2010. CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients. Immunity 32:129.

    Not in our library10.1016/j.immuni.2009.11.009

51. 51.

    Iwata Y. Matsushita T. Horikawa M.. 2011. Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 117:530.

    Not in our library10.1182/blood-2010-07-294249

52. 52.

    Lindner S. Dahlke K. Sontheimer K.. 2013. Interleukin 21-induced granzyme B-expressing B cells infiltrate tumors and regulate T cells. Cancer Res. 73:2468.

    Not in our library10.1158/0008-5472.can-12-3450

53. 53.

    van de Veen W. Stanic B. Yaman G.. 2013. IgG4 production is confined to human IL-10-producing regulatory B cells that suppress antigen-specific immune responses. J. Allergy Clin. Immunol. 131:1204.

    Not in our library10.1016/j.jaci.2013.01.014

54. 54.

    Saze Z. Schuler P. J. Hong C. S. Cheng D. Jackson E. K. and Whiteside T. L. 2013. Adenosine production by human B cells and B cell-mediated suppression of activated T cells. Blood 122:9.

    Not in our library10.1182/blood-2013-02-482406

55. 55.

    Nouël A. Pochard P. Simon Q.. 2015. B-Cells induce regulatory T cells through TGF-β/IDO production in A CTLA-4 dependent manner. J. Autoimmun. 59:53.

    Not in our library10.1016/j.jaut.2015.02.004

56. 56.

    Flores-Borja F. Bosma A. Ng D.. 2013. CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci. Transl. Med. 5:173ra23.

    Not in our library10.1126/scitranslmed.3005407

57. 57.

    Bosma A. Abdel-Gadir A. Isenberg D. A. Jury E. C. and Mauri C. 2012. Lipid-antigen presentation by CD1d(+) B cells is essential for the maintenance of invariant natural killer T cells. Immunity 36:477.

    Not in our library10.1016/j.immuni.2012.02.008

58. 58.

    Anolik J. H. Barnard J. Owen T.. 2007. Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy. Arthritis Rheum. 56:3044.

    Not in our library10.1002/art.22810

59. 59.

    Palanichamy A. Barnard J. Zheng B.. 2009. Novel human transitional B cell populations revealed by B cell depletion therapy. J. Immunol. 182:5982.

    Not in our library10.4049/jimmunol.0801859

60. 60.

    Siewe B. Stapleton J. T. Martinson J.. 2013. Regulatory B cell frequency correlates with markers of HIV disease progression and attenuates anti-HIV CD8⁺ T cell function in vitro. J. Leukoc. Biol. 93:811.

    Not in our library10.1189/jlb.0912436

61. 61.
    Regulatory B cells inhibit cytotoxic T lymphocyte (CTL) activity and elimination of infected CD4 T cells after in vitro reactivation of HIV latent reservoirs. · 2014

    Not checked
62. 62.
    Regulatory B cells: an exciting target for future therapeutics in transplantation · 2014

    Not checked
63. 63.

    Khoder A. Sarvaria A. Alsuliman A.. 2014. Regulatory B cells are enriched within the IgM memory and transitional subsets in healthy donors but are deficient in chronic GVHD. Blood 124:2034.

    Not in our library10.1182/blood-2014-04-571125

64. 64.

    Newell K. A. Asare A. Kirk A. D..; Immune Tolerance Network ST507 Study Group. 2010. Identification of a B cell signature associated with renal transplant tolerance in humans. J. Clin. Invest. 120:1836.

    Not in our library10.1172/jci39933

65. 65.

    Cherukuri A. Rothstein D. M. Clark B.. 2014. Immunologic human renal allograft injury associates with an altered IL-10/TNF-α expression ratio in regulatory B cells. J. Am. Soc. Nephrol. 25:1575.

    Not in our library10.1681/asn.2013080837

66. 66.

    Shabir S. Girdlestone J. Briggs D.. 2015. Transitional B lymphocytes are associated with protection from kidney allograft rejection: a prospective study. Am. J. Transplant. 15:1384.

    Not in our library10.1111/ajt.13122

67. 67.

    Rosser E. C. Oleinika K. Tonon S.. 2014. Regulatory B cells are induced by gut microbiota-driven interleukin-1β and interleukin-6 production. Nat. Med. 20:1334.

    Not in our library10.1038/nm.3680

68. 68.

    Schubert R. D. Hu Y. Kumar G.. 2015. IFN-β treatment requires B cells for efficacy in neuroautoimmunity. J. Immunol. 194:2110

    Not in our library10.4049/jimmunol.1402029

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