MOJ eISSN: 2373-4442 MOJI

Short Communication
Volume 1 Issue 1 - 2014
IL-10 Producing Regulatory B cells: Where Are We?
Jean-David Bouaziz1,2,3, Adele de Masson1,2,3, Martine Bagot1,2,3 and Armand Bensussan1,2*
1INSERM U976, Hopital Saint Louis, France
2Laboratory of Onco-Dermatology, Immunology & Cutaneous Stem Cells, Paris Diderot University, France
3Department of Dermatology, Hopital Saint Louis, France
Received: April 25, 2014 | Published: April 29, 2014
*Corresponding author: Armand Bensussan, Hopital Saint Louis, INSERM U976, Equerre Bazin, 1 avenue Claude Vellefaux, F-75010, Paris, France, Tel: +331-537-220-81; Fax: +331-537-220-51; Email:
Citation: Bouaziz JD, de Masson A, Bagot M, Bensussan A (2014) IL-10 Producing Regulatory B cells: Where Are We?. MOJ Immunol 1(1): 00003. DOI: 10.15406/moji.2014.01.00003


B cells have long been only considered as effector cells during the specific immune response because of antibody production and antigen presentation to T cells. Recently growing evidence has shown that B cells are also able to secrete proinflammatory cytokines as well as the anti-inflammatory cytokine IL-10. IL-10-producing regulatory B cells (Bregs) and more recently IL-10 producing plasma cells have been undoubtedly identified in mice and shown to down-regulate inflammation. Several recent works have also identified IL-10 producing regulatory B cells in humans and have begun to unravel their phenotype and mode of suppression. Future work should explore whether a specific transcriptional factor drives the natural fate of Bregs or whether IL-10 producing B cells only emerge from any B cell subset in response to specific inflammatory signals.
Keywords: B cell; Plasma cell; Interleukin-10; Tolerance

B cells were first recognized for their role as positive regulators of immune responses in immunity, because they can give rise to antibody-producing plasma cells and contribute to CD4+ T cell responses. The B cells carrying these functions can be commonly designated as effector B cells. Recent studies have indicated that B cells also play a role as negative regulators of immune response in autoimmunity, these properties being mainly attributed to the latterly described interleukin 10 (IL-10) regulatory B cell (Breg) compartment [1,2]. Bregs play key roles in immune tolerance and their absence results in exacerbation of auto-immunity [3-7], graft-versus-host disease [8] and impaired anti-tumor immune response [9]. The first assumption that B cells may have a suppressive role wass made in the early seventies in a contact dermatitis mouse model. In this study, adoptively transferred whole splenocytes but not adoptively transferred B cell depleted splenocytes had a suppressive effect in vivo [10]. In mouse models of inflammation key experiments demonstrated the negative regulatory role of IL-10 producing B cells. Janeway et al [5] have shown that B cells had regulatory properties in a mouse model of experimental autoimmune encephalomyelitis (EAE) [5]. Later, the regulatory properties of these B cells were linked to their ability to produce IL-10 [3]: bone marrow chimeras with IL-10 deficient B cells have more severe autoimmune encephalomyelitis (EAE) (“B cells regulate autoimmunity by provision of IL-10”). Mizoguchi et al [11] demonstrated that chronic intestinal inflammation generates IL-10 producing B cells in mesenteric lymph nodes and that these IL-10 producing B cells suppressed inflammatory bowel disease [11]. Mauri et al [7] described that repeated adoptive transfer of CD40-activated B cells (IL-10 producing B cells) reduced the severity of collagen-induced arthritis in mice [7]. Finally, Tedder group showed in several publications that adoptive transfer of IL-10 producing B cells that displayed a CD5+CD1dhi phenotype (called “B10” cells) could diminish inflammation in mouse models of contact dermatitis [6], EAE [12] and lupus [13]. The most recent findings about the biology of Bregs in mice include: i/ the crucial role of interleukin 21 in the in vitro generation of IL-10 producing B cells [14], ii/ the emerging concept that plasma cells derived from B cells play a key role in vivo in the regulatory function of the B cell lineage through IL-10 and IL-35 cytokine production [15]. We and others have also identified IL-10 producing regulatory B cells in humans and have begun to unravel their phenotype and mode of suppression. Cell surface phenotype of human Bregs mainly includes CD24highCD27+ B cell subset [16, 17] and CD24highCD38high transitional blood B cell subset [18]. Mechanisms of suppression may imply inhibition of CD4+ T proliferation, inhibition of Th1 differentiation, induction of regulatory T cells and suppression of monocyte activation. Recently diminished frequency and/or a diminished suppressive capacity of Bregs have been demonstrated in patients with lupus [18], immune thrombocytopenia [19], rheumatoid arthritis [20] and ANCA-associated vasculitis [21]. However the exact mechanism of how human Bregs exert their regulatory functions in vivo remains unclear. Future work should explore whether a specific transcriptional factor drives the natural fate of Bregs or whether IL-10 producing B cells only emerge from any B cell subset in response to specific inflammatory signals.


  1. Mauri C, Bosma (2012) A Immune regulatory function of B cells.  Ann Rev Immunol 30: 221-241.
  2. Bouaziz JD, Yanaba K, Tedder TF (2008) Regulatory B cells as inhibitors of immune responses and inflammation. Immunol Rev 224: 201-214.
  3. Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM (2002) B cells regulate autoimmunity by provision of IL-10. Nature Immunology 3: 944-950.
  4. Mizoguchi A, Mizoguchi E, Smith RN, Preffer FI, Bhan AK (1997) Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice. J Exp Med 186(10): 1749-1756.
  5. Wolf SD, Dittel BN, Hardardottir F, Janeway CA (1996) Experimental autoimmune encephalomyelitis induction in genetically B cell-deficient mice. J Exp Med 184(6): 2271-2278.
  6. Yanaba K, Bouaziz JD, Haas KM, Poe JC, Fujimoto M, et al. (2008) A regulatory B cell subset with a unique CD1dhiCD5+phenotype controls T cell-dependent inflammatory responses. Immunity 28(5): 639-650.
  7. Mauri C, Gray D, Mushtaq N, Londei M (2003) Prevention of arthritis by interleukin 10-producing B cells. J Exp Med 197(4): 489-501.
  8. Rowe V, Banovic T, MacDonald KP, Kuns R, Don AL, et al. (2006) Host B cells produce IL-10 following TBI and attenuate acute GVHD after allogeneic bone marrow transplantation. Blood 108(7): 2485-2492.
  9. Inoue S, Leitner WW, Golding B, Scott D (2006) Inhibitory effects of B cells on antitumor immunity. Cancer Res 66(15): 7741-7747.
  10. Katz SI, Parker D, Turk JL (1974) B-cell suppression of delayed hypersensitivity reactions. Nature 251: 550-551.
  11. Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK (2002) Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity 16(2): 219-230.
  12. 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 Invest 118(10): 3420-3430.
  13. 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(9): 4801-4809.
  14. 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(7423): 264-268.
  15. 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(7492): 366-370.
  16. Bouaziz JD, Calbo S, Maho-Vaillant M, Saussine A, Bagot M, et al. (2010) IL10 produced by activated human B cells regulates CD4(+) T-cell activation in vitro. Eur J Immunol 40(10): 2686-2691.
  17. 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(2): 530-541.
  18. Blair PA, Norena LY, Flores Borja F, Rawlings DJ, Isenberg DA, et al. (2010) CD19+CD24hiCD38hi B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in Systemic Lupus Erythematosus patients. Immunity 32(1): 129-140.
  19. Li X, Zhong H, Bao W, Boulad N, Evangelista J, et al. (2012) Defective regulatory B-cell compartment in patients with immune thrombocytopenia. Blood 120(16): 3318-3325.
  20. Flores-Borja F1, Bosma A, Ng D, Reddy V, Ehrenstein MR, et al. (2013) CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH2 differentiation. Sci Transl Med 5(173): 173ra23.
  21. Wilde B, Thewissen M, Damoiseaux J, Knippenberg S, Hilhorst M, et al. (2013) Regulatory B cells in ANCA-associated vasculitis. Ann Rheum Dis 72(8): 1416-1419.
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