Mediterr J Rheumatol 2017;28(2):75-9
Regulatory B cells in autoimmune rheumatic diseases
Authors Information
Department of Rheumatology and Clinical Immunology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece
  1. Mauri C, Gray D, Mushtaq N, Londei M. Prevention of arthritis by interleukin 10-producing B cells. J Exp Med 2003;197:489-501.
  2. Horikawa M, Minard-Colin V, Matsushita T, Tedder T F. Regulatory B cell production of IL-10 inhibits lymphoma depletion during CD20 immunotherapy in mice. J Clin Invest 2011;121:4268-80.
  3. Iwata Y, Matsushita T, Horikawa M, Dilillo DJ, Yanaba K, Venturi G M, et al. Characterization of a rare IL10-competent B cell-cell subset in humans that parallels mouse regulatory B10 cells. Blood 2011 Jan 13;117:530-41.
  4. Matsushita T, Horikawa M, Iwata Y, Tedder T F. Regulatory B cells (B10 cells) and regulatory T cells have independent roles in controlling experimental autoimmune encephalomyelitis initiation and late-phase immuopathogenesis. J Immunol 2010;185:2240-52.
  5. Sarvaria A, Basar R, Mehta R S, Shaim H, Muftuoglu M, Khoder A, et al. IL-10+ regulatory B cells are enriched in cord blood and may protect against cGVHD after cord blood transplantation. Blood 2016;128:1346-61.
  6. Yoshizaki A, Miyagaki T, DiLillo D J, Matsushita T, Horikawa M, Kountikov E I, et al. Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature 2012;491:264-8.
  7. Rosser E C, Mauri C. Regulatory B cells: Origin, phenotype, and function. Immunity 2015;42:607-12.
  8. Noh J, Choi W S, Noh G, Lee J H. Presence of Foxp3-expressing CD19(+)CD5(+) B Cells in Human Peripheral Blood Mononuclear Cells: Human CD19(+)CD5(+)Foxp3(+) Regulatory B Cell (Breg). Immune Netw 2010;10:247-9.
  9. Ray A, Wang L, Dittel B N. IL-10-independent regulatory B-cell subsets and mechanisms of action. Int Immunol 2015;27:531-6.
  10. Shen P, Roch T, Lampropoulou V, O’Connor RA, Stervbo U, Hilgenberg E, et al. IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature 2014;507:366-70.
  11. Bjarnadottir K, Benkhoucha M, Merkler D, Weber M S, Rayne N L, Bernard C C, et al. B cell-derived transforming growth factor-β1 expression limits the induction phase of autoimmune neuroinflammation. Sci Rep 2016;6:34594.
  12. Kalampokis I, Venturi G M, Poe J C, Dvergsten J A, Sleasman J W, Tedder T F. The regulatory B cell compartment expands transiently during childhood and is contracted in children with autoimmunity. Arthritis Rheumatol 2017;184:48-53. https://doi.org/10.1002/art.39820
  13. Duggal N A, Upton J, Phillips A C, Sapey E, Lord J M. An age-related numerical and functional deficit in CD19(+) CD24(hi) CD38(hi) B cells is associated with an increase in systemic autoimmunity. Aging Cell 2013;12:873-81.
  14. Hua C, Audo R, Yeremenko N, Baeten D, Hahne M, Combe B, et al. A proliferation inducing ligand (APRIL) promotes IL-10 production and regulatory functions of human B cells. J Autoimmun 2016;73:64-72.
  15. Park M K, Jung Y O, Lee S Y, Lee S H, Heo Y J, Kim E K, et al. Amelioration of autoimmune arthritis by adoptive transfer of Foxp3-expressing regulatory B cells is associated with Treg/Th17 cell balance. J Transl Med 2016;14:191.
  16. Blair P A, Noreña L Y, Flores-Borja F, Rawlings D J, Isenberg D A, Ehrenstein M R, 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;32:129-40.
  17. Flores-Borja F, Bosma A, Ng D, Reddy V, Ehrenstein M R, Isenberg D A, et al. CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci Transl Med 2013;5:173ra23.
  18. Jeong Y I, Hong S H, Cho S H, Lee W J, Lee  SE. Induction of IL-10-producing CD1dhighCD5+ regulatory B cells following Babesia microti-infection. PLoS One 2012;7:e46553.
  19. Ding Q, Yeung M, Camirand G, Zeng Q, Akiba H, Yagita H, et al. 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 2011;121:3645-56.
  20. Kessel A, Haj T, Peri R, Snir A, Melamed D, Sabo E, et al. Human CD19+CD25high B regulatory cells suppress proliferation of CD4+ T cells and enhance Foxp3 and CTLA-4 expression in T-regulatory cells. Autoimmun Rev 2012;11:670-7.
  21. Daien C I, Gailhac S, Mura T, Audo R, Combe B, Hahne M, et al. Regulatory B10 cells are decreased in patients with rheumatoid arthritis and are inversely correlated with disease activity. Arthritis Rheumatol 2014;66:2037-46.
  22. 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;33:187-95.
  23. Guo Y, Zhang X, Qin M, Wang X. Changes in peripheral CD19(+)Foxp3(+) and CD19(+)TGFb(+) regulatory b cell populations in rheumatoid arthritis patients with interstitial lung disease. J Thorac Dis 2015;7:471-7.
  24. Cui D, Zhang L, Chen J, Zhu M, Hou L, Chen B, et al. Changes in regulatory b cells and their relationship with rheumatoid arthritis disease activity. Clin Exp Med 2015 Aug;15:285-92.
  25. Kim J, Lee H J, Yoo I S, Kang S W, Lee J H. Regulatory B cells are inversely correlated with disease activity in rheumatoid arthritis. Yonsei Med J 2014;55:1354-8.
  26. Jin L, Weiqian C, Lihuan Y. Peripheral CD24hi CD27+ CD19+ B cells subset as a potential biomarker in naïve systemic lupus erythematosus. Int J Rheum Dis. 2013;16(6):698-708.
  27. Menon M, Blair P A, Isenberg D A, Mauri C. A Regulatory Feedback between Plasmacytoid Dendritic Cells and Regulatory B Cells Is Aberrant in Systemic Lupus Erythematosus. Immunity 2016;44:683-97.
  28. Heinemann K, Wilde B, Hoerning A, Tobbe B, Kribben A, Witzke O, et al. Decreased IL-10(+) regulatory B cells (Bregs) in lupus nephritis patients. Scand J Rheumatol 2016;45:312-6.
  29. Gao N, Dresel J, Eckstein V, Gellert R, Störch H, Venigalla R K C, et al. Impaired suppressive capacity of activation-induced regulatory B cells in systemic lupus erythematosus. Arthritis Rheumatol 2014;66:2849-61.
  30. Yang X, Yang J, Chu Y, Xue Y, Xuan D, Zheng S, et al. T follicular helper cells and regulatory B cell dynamics in systemic lupus erythematosus. PLoS One 2014;9:e88441.
  31. Vadasz Z, Peri R, Eiza N, Slobodin G, Balbir-Gurman A, Toubi E. The Expansion of CD25 high IL-10 high FoxP3 high B Regulatory Cells Is in Association with SLE Disease Activity. J Immunol Res 2015;2015:254245.
  32. Watanabe R, Ishiura N, Nakashima H, Kuwano Y, Okochi H, Tamaki K, et al. Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity. J Immunol 2010;184:4801-9.
  33. Scapini P, Lamagna C, Hu Y, Lee K, Tang Q, DeFranco A L, et al. B cell-derived IL-10 suppresses inflammatory disease in Lyn-deficient mice. Proc Natl Acad Sci U S A 2011;108(41):E823-32.
  34. Cai Z, Wong C K, Dong J, Chu M, Jiao D, Kam N W, et al. Remission of systemic lupus erythematosus disease activity with regulatory cytokine interleukin (IL)-35 in Murphy Roths Large (MRL)/lpr mice. Clin Exp Immunol 2015;181:253-66.
  35. Furuzawa-Carballeda J, Hernadez-Molina G, Lima G, Rivera-Vicencio Y, Ferez-Blando K, Liorente L. Peripheral regulatory cells immunophenotyping in primary Sjögren's syndrome: a cross-sectional study. Arthritis Res Ther 2013;15:R68.
  36. Lin W, Jin L, Chen H, Wu Q, Fei Y, Zheng W, et al. B cell subsets and dysfunction of regulatory B cells in IgG4-related disease and primary Sjögren’s syndrome: The similarities and differences. Arthritis Res Ther. 2014;16:R118.
  37. Bunch D O, McGregor J G, Khandoobhai N B, Aybar L T, Burkart M E, Hu Y, et al. Decreased CD5⁺ B cells in active ANCA vasculitis and relapse after rituximab. Clin J Am Soc Nephrol 2013;8:382-91.
  38. Wilde B, Thewissen M, Damoiseaux J, Knippenberg S, Hilhorst M, van Paassen P, et al. Regulatory B cells in ANCA-associated vasculitis. Ann Rheum Dis 2013;72:1416-9.
  39. Aybar L T, McGregor J G, Hogan S L, Hu Y, Mendoza C E, Brand E J, et al. Reduced CD5(+) CD24(hi) CD38(hi) and interleukin-10(+) regulatory B cells in active anti-neutrophil cytoplasmic autoantibody-associated vasculitis permit increased circulating autoantibodies. Clin Exp Immunol 2015;180:178-88.
  40. Lepse N, Abdulahad W H, Rutgers A, Kallenberg C G, Stegeman C A, Heeringa P. Altered B cell balance, but unaffected B cell capacity to limit monocyte activation in anti-neutrophil cytoplasmic antibody-associated vasculitis in remission. Rheumatology (Oxford) 2014;53:1683-92.
  41. Todd S K, Pepper R J, Draibe J, Tanna A, Pusey C D, Mauric C, et al. Regulatory B cells are numerically but not functionally deficient in anti-neutrophil cytoplasm antibody-associated vasculitis. Rheumatology 2014;53:1693-703.
  42. Hu X, Tai J, Qu Z, Zhao S, Zhang L, Li M, et al. A lower proportion of regulatory B cells in patients with Henoch-Schoenlein purpura nephritis. PLoS One. 2016;11:e0152368.
  43. van der Geest KS, Abdulahad WH, Chalan P, Rutgers A, Horst G, Huitena MG, et al. Disturbed B cell homeostasis in newly diagnosed giant cell arteritis and polymyalgia rheumatica. Arthritis Rheumatol 2014;66:1927-38.
  44. Li W, Tian X, Lu X, Peng Q, Shu X, Yang H, et al. Significant decrease in peripheral regulatory B cells is an immunopathogenic feature of dermatomyositis. Sci Rep 2016;6:27479.
  45. Sakkas L I, Chikanza I C, Platsoucas C D. Mechanisms of Disease: the role of immune cells in the pathogenesis of systemic sclerosis. Nat Clin Pract Rheumatol 2006;2:679-85.
  46. Sakkas L I, Bogdanos D P. Systemic sclerosis: New evidence re-enforces the role of B cells. Autoimmun Rev 2016;15:155-61.
  47. Mavropoulos A, Simopoulou T, Varna A, Liaskos C, Katsiari C G, Bogdanos D P, et al. Breg Cells Are Numerically Decreased and Functionally Impaired in Patients With Systemic Sclerosis. Arthritis Rheumatol 2016;68:494-504.
  48. 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;55:263-7.
  49. Korniotis S, Gras C, Letscher H, Montandon R, Megret J, Siegert S, et al. Treatment of ongoing autoimmune encephalomyelitis with activated B-cell progenitors maturing into regulatory B cells. Nat Commun 2016;7:12134.
  50. Park M J, Kwok S K, Lee S H, Kim E K, Park S H, Cho M L. Adipose tissue-derived mesenchymal stem cells induce expansion of interleukin-10-producing regulatory B cells and ameliorate autoimmunity in a murine model of systemic lupus erythematosus. Cell Transplant 2015;24:2367-77.