MOJ ISSN: 2373-4442MOJI

Immunology
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: armand.bensussan@inserm.fr
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

Abstract

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.

References

  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.
© 2014-2016 MedCrave Group, All rights reserved. No part of this content may be reproduced or transmitted in any form or by any means as per the standard guidelines of fair use.
Creative Commons License Open Access by MedCrave Group is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work at http://medcraveonline.com
Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version | Opera |Privacy Policy