Human regulatory B cells in health and disease: Therapeutic potential

Journal of Clinical Investigation

Volumn 127, Issue 3, 2017, Pages 772-779

  Mauri, Claudia ^a   Menon, Madhvi ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALEMTUZUMAB; BETA INTERFERON; FINGOLIMOD; INTERLEUKIN 10; INTERLEUKIN 6; RITUXIMAB; IL10 PROTEIN, HUMAN;

ALLERGY; AUTOIMMUNE DISEASE; AUTOIMMUNITY; B LYMPHOCYTE; B LYMPHOCYTE DIFFERENTIATION; CELL PLASTICITY; HEALTH; HUMAN; IMMUNE DEFICIENCY; IMMUNE RESPONSE; IMMUNOMODULATION; IMMUNOTHERAPY; INFECTION; INFLAMMATION; INFLAMMATORY BOWEL DISEASE; LYMPHOCYTE DEPLETION; LYMPHOCYTE FUNCTION; LYMPHOCYTE SUBPOPULATION; LYMPHOCYTE TRANSFER; MALIGNANT NEOPLASM; MULTIPLE SCLEROSIS; NONHUMAN; PEMPHIGUS; PHENOTYPE; REVIEW; RHEUMATOID ARTHRITIS; SYSTEMIC LUPUS ERYTHEMATOSUS; TRANSPLANTATION; TUMOR GROWTH; ANIMAL; IMMUNE SYSTEM DISEASES; IMMUNOLOGY; PATHOLOGY; PROCEDURES; REGULATORY B LYMPHOCYTE;

ANIMALS; B-LYMPHOCYTES, REGULATORY; HUMANS; IMMUNE SYSTEM DISEASES; IMMUNOTHERAPY; INTERLEUKIN-10;

EID: 85015911678     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI85113     Document Type: Review

References (85)

1. Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell. 2010;140(6):771-776.
2. Moudgil KD, Choubey D. Cytokines in autoimmunity: role in induction, regulation, and treatment. J Interferon Cytokine Res. 2011;31(10):695-703.
3. Chaudhry A, Rudensky AY. Control of inflammation by integration of environmental cues by regulatory T cells. J Clin Invest. 2013;123(3):939-944.
4. Blair PA, et al. CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity. 2010;32(1):129-140.
5. Carter NA, et al. 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. 2011;186(10):5569-5579.
6. Flores-Borja F, et al. CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci Transl Med. 2013;5(173):173ra23.
7. Khoder A, et al. Regulatory B cells are enriched within the IgM memory and transitional subsets in healthy donors but are deficient in chronic GVHD. Blood. 2014;124(13):2034-2045.
8. van der Vlugt LE, et al. CD24(hi)CD27(+) B cells from patients with allergic asthma have impaired regulatory activity in response to lipopolysaccharide. Clin Exp Allergy. 2014;44(4):517-528.
9. Kamekura R, et al. Alteration of circulating type 2 follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma. Clin Immunol. 2015;158(2):204-211.
10. Zhu HQ, et al. Impaired function of CD19(+) CD24(hi) CD38(hi) regulatory B cells in patients with pemphigus. Br J Dermatol. 2015;172(1):101-110.
11. Oka A, et al. Role of regulatory B cells in chronic intestinal inflammation: association with pathogenesis of Crohn's disease. Inflamm Bowel Dis. 2014;20(2):315-328.
12. Mauri C, Menon M. The expanding family of regulatory B cells. Int Immunol. 2015;27(10):479-486.
13. Iwata Y, et al. Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood. 2011;117(2):530-541.
14. Lindner S, et al. Interleukin 21-induced granzyme B-expressing B cells infiltrate tumors and regulate T cells. Cancer Res. 2013;73(8):2468-2479.
15. Matsumoto M, et al. Interleukin-10-producing plasmablasts exert regulatory function in autoimmune inflammation. Immunity. 2014;41(6):1040-1051.
16. Liu J, et al. IL-10-producing B cells are induced early in HIV-1 infection and suppress HIV-1-specific T cell responses. PLoS One. 2014;9(2):e89236.
17. Das A, et al. IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection. J Immunol. 2012;189(8):3925-3935.
18. Menon M, Blair PA, Isenberg DA, Mauri C. A regulatory feedback between plasmacytoid dendritic cells and regulatory B cells is aberrant in systemic lupus erythematosus. Immunity. 2016;44(3):683-697.
19. van de Veen W, et al. IgG4 production is confined to human IL-10-producing regulatory B cells that suppress antigen-specific immune responses. J Allergy Clin Immunol. 2013;131(4):1204-1212.
20. Nouël A, et al. B-Cells induce regulatory T cells through TGF-β/IDO production in A CTLA-4 dependent manner. J Autoimmun. 2015;59:53-60.
21. Bosma A, Abdel-Gadir A, Isenberg DA, Jury EC, Mauri C. Lipid-antigen presentation by CD1d(+) B cells is essential for the maintenance of invariant natural killer T cells. Immunity. 2012;36(3):477-490.
22. Saze Z, Schuler PJ, Hong CS, Cheng D, Jackson EK, Whiteside TL. Adenosine production by human B cells and B cell-mediated suppression of activated T cells. Blood. 2013;122(1):9-18.
23. Shen P, et al. IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature. 2014;507(7492):366-370.
24. Baba Y, Matsumoto M, Kurosaki T. Signals controlling the development and activity of regulatory B-lineage cells. Int Immunol. 2015;27(10):487-493.
25. Knippenberg S, et al. Reduction in IL-10 producing B cells (Breg) in multiple sclerosis is accompanied by a reduced naïve/memory Breg ratio during a relapse but not in remission. J Neuroimmunol. 2011;239(1-2):80-86.
26. Hayashi M, et al. IL-10-producing regulatory B cells are decreased in patients with psoriasis. J Dermatol Sci. 2016;81(2):93-100.
27. Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM. B cells regulate autoimmunity by provision of IL-10. Nat Immunol. 2002;3(10):944-950.
28. Carter NA, Rosser EC, Mauri C. 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. Arthritis Res Ther. 2012;14(1):R32.
29. Mauri C, Gray D, Mushtaq N, Londei M. Prevention of arthritis by interleukin 10-producing B cells. J Exp Med. 2003;197(4):489-501.
30. Blair PA, et al. Selective targeting of B cells with agonistic anti-CD40 is an efficacious strategy for the generation of induced regulatory T2-like B cells and for the suppression of lupus in MRL/lpr mice. J Immunol. 2009;182(6):3492-3502.
31. 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(10):3420-3430.
32. Rosser EC, et al. Regulatory B cells are induced by gut microbiota-driven interleukin-1 and interleukin-6 production. Nat Med. 2014;20(11):1334-1339.
33. Yoshizaki A, et al. Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature. 2012;491(7423):264-268.
34. Correale J, Farez M, Razzitte G. Helminth infections associated with multiple sclerosis induce regulatory B cells. Ann Neurol. 2008;64(2):187-199.
35. Schubert RD, et al. IFN treatment requires B cells for efficacy in neuroautoimmunity. J Immunol. 2015;194(5):2110-2116.
36. Grützke B, et al. Fingolimod treatment promotes regulatory phenotype and function of B cells. Ann Clin Transl Neurol. 2015;2(2):119-130.
37. Thompson SA, Jones JL, Cox AL, Compston DA, Coles AJ. B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of multiple sclerosis. J Clin Immunol. 2010;30(1):99-105.
38. Heidt S, Hester J, Shankar S, Friend PJ, Wood KJ. B cell repopulation after alemtuzumab induction-transient increase in transitional B cells and long-term dominance of naïve B cells. Am J Transplant. 2012;12(7):1784-1792.
39. Barr TA, et al. B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6-producing B cells. J Exp Med. 2012;209(5):1001-1010.
40. Heinemann K, et al. Decreased IL-10(+) regulatory B cells (Bregs) in lupus nephritis patients. Scand J Rheumatol. 2016;45(4):312-316.
41. Gao N, et al. Impaired suppressive capacity of activation-induced regulatory B cells in systemic lupus erythematosus. Arthritis Rheumatol. 2014;66(10):2849-2861.
42. Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Immunology. 2014;14(1):36-49.
43. Ramos-Casals M, Soto MJ, Cuadrado MJ, Khamashta MA. Rituximab in systemic lupus erythematosus: A systematic review of off-label use in 188 cases. Lupus. 2009;18(9):767-776.
44. Aguiar R, Araujo C, Martins-Coelho G, Isenberg D. Use of rituximab in systemic lupus erythematosus: a single center experience over 14 years [published online ahead of print April 25, 2016]. Arthritis Care Res (Hoboken). https://doi.org/10.1002/acr.22921.
45. Anolik JH, et al. Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy. Arthritis Rheum. 2007;56(9):3044-3056.
46. Palanichamy A, et al. Novel human transitional B cell populations revealed by B cell depletion therapy. J Immunol. 2009;182(10):5982-5993.
47. Wermeling F, Lind SM, Jordö ED, Cardell SL, Karlsson MC. Invariant NKT cells limit activation of autoreactive CD1d-positive B cells. J Exp Med. 2010;207(5):943-952.
48. Daien CI, et al. Regulatory B10 cells are decreased in patients with rheumatoid arthritis and are inversely correlated with disease activity. Arthritis Rheum. 2014;66(8):2037-2046.
49. Ma L, Liu B, Jiang Z, Jiang Y. Reduced numbers of regulatory B cells are negatively correlated with disease activity in patients with new-onset rheumatoid arthritis. Clin Rheumatol. 2014;33(2):187-195.
50. Cui D, et al. Changes in regulatory B cells and their relationship with rheumatoid arthritis disease activity. Clin Exp Med. 2015;15(3):285-292.
51. Kim J, Lee HJ, Yoo IS, Kang SW, Lee JH. Regulatory B cells are inversely associated with disease activity in rheumatoid arthritis. Yonsei Med J. 2014;55(5):1354-1358.
52. Amagai M. Pemphigus: autoimmunity to epidermal cell adhesion molecules. Adv Dermatol. 1996;11:319-352; discussion 353.
53. Colliou N, et al. Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response. Sci Transl Med. 2013;5(175):175ra30.
54. Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol. 2010;28:573-621.
55. Kleffel S, et al. Interleukin-10+ regulatory B cells arise within antigen-experienced CD40+ B cells to maintain tolerance to islet autoantigens. Diabetes. 2015;64(1):158-171.
56. Mavropoulos A, et al. Breg cells are numerically decreased and functionally impaired in patients with systemic sclerosis. Arthritis Rheum. 2016;68(2):494-504.
57. Matsushita T, Hamaguchi Y, Hasegawa M, Takehara K, Fujimoto M. Decreased levels of regulatory B cells in patients with systemic sclerosis: association with autoantibody production and disease activity. Rheumatology (Oxford). 2016;55(2):263-267.
58. Shen P, Fillatreau S. Suppressive functions of B cells in infectious diseases. Int Immunol. 2015;27(10):513-519.
59. Siewe B, et al. Regulatory B cell frequency correlates with markers of HIV disease progression and attenuates anti-HIV CD8+ T cell function in vitro. J Leukoc Biol. 2013;93(5):811-818.
60. Siewe B, et al. Regulatory B cells inhibit cytotoxic T lymphocyte (CTL) activity and elimination of infected CD4 T cells after in vitro reactivation of HIV latent reservoirs. PLoS One. 2014;9(4):e92934.
61. Liu Y, et al. IL-10-producing regulatory B-cells suppressed effector T-cells but enhanced regulatory T-cells in chronic HBV infection. Clin Sci. 2016;130(11):907-919.
62. Lee JH, et al. Allergen-specific B cell subset responses in cow's milk allergy of late eczematous reactions in atopic dermatitis. Cell Immunol. 2010;262(1):44-51.
63. Noh J, et al. Characterisation of allergen-specific responses of IL-10-producing regulatory B cells (Br1) in Cow Milk Allergy. Cell Immunol. 2010;264(2):143-149.
64. Olkhanud PB, et al. Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4+ T cells to T-regulatory cells. Cancer Res. 2011;71(10):3505-3515.
65. Zhang Y, Gallastegui N, Rosenblatt JD. Regulatory B cells in anti-tumor immunity. Int Immunol. 2015;27(10):521-530.
66. Wejksza K, et al. Cancer-produced metabolites of 5-lipoxygenase induce tumor-evoked regulatory B cells via peroxisome proliferator-activated receptor ?. J Immunol. 2013;190(6):2575-2584.
67. Han S, et al. Glioma cell-derived placental growth factor induces regulatory B cells. Int J Biochem Cell Biol. 2014;57:63-68.
68. Horikawa M, Minard-Colin V, Matsushita T, Tedder TF. Regulatory B cell production of IL-10 inhibits lymphoma depletion during CD20 immunotherapy in mice. J Clin Invest. 2011;121(11):4268-4280.
69. Nouël A, Simon Q, Jamin C, Pers JO, Hillion S. Regulatory B cells: an exciting target for future therapeutics in transplantation. Front Immunol. 2014;5:11.
70. Newell KA, et al. Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest. 2010;120(6):1836-1847.
71. Cherukuri A, et al. Immunologic human renal allograft injury associates with an altered IL-10/TNF-α expression ratio in regulatory B cells. J Am Soc Nephrol. 2014;25(7):1575-1585.
72. Shabir S, et al. Transitional B lymphocytes are associated with protection from kidney allograft rejection: a prospective study. Am J Transplant. 2015;15(5):1384-1391.
73. Sarvaria A, et al. IL-10+ regulatory B cells are enriched in cord blood and may play a role in protection against GVHD after cord blood transplantation. Blood. 2016;128(10):1346-1361.
74. Okur FV, Brenner MK. Cellular immunotherapy of cancer. Methods Mol Biol. 2010;651:319-345.
75. Miyagaki T, Fujimoto M, Sato S. Regulatory B cells in human inflammatory and autoimmune diseases: from mouse models to clinical research. Int Immunol. 2015;27(10):495-504.
76. 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(2):219-230.
77. Yamamoto R, et al. PD-1-PD-1 ligand interaction contributes to immunosuppressive microenvironment of Hodgkin lymphoma. Blood. 2008;111(6):3220-3224.
78. Ansell SM, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372(4):311-319.
79. Armand P, et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial. J Clin Oncol. 2013;31(33):4199-4206.
80. Rafei M, et al. A granulocyte-macrophage colony-stimulating factor and interleukin-15 fusokine induces a regulatory B cell population with immune suppressive properties. Nat Med. 2009;15(9):1038-1045.
81. Yang M, et al. Novel function of B cell-activating factor in the induction of IL-10-producing regulatory B cells. J Immunol. 2010;184(7):3321-3325.
82. Genestier L, Taillardet M, Mondiere P, Gheit H, Bella C, Defrance T. TLR agonists selectively promote terminal plasma cell differentiation of B cell subsets specialized in thymus-independent responses. J Immunol. 2007;178(12):7779-7786.
83. Grammer AC, Lipsky PE. CD154-CD40 interactions mediate differentiation to plasma cells in healthy individuals and persons with systemic lupus erythematosus. Arthritis Rheum. 2002;46(6):1417-1429.
84. Wang RX, et al. Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat Med. 2014;20(6):633-641.
85. Maseda D, et al. Regulatory B10 cells differentiate into antibody-secreting cells after transient IL-10 production in vivo. J Immunol. 2012;188(3):1036-1048.