IL-10 Producing Regulatory B cells: Where Are We?

doi:10.15406/moji.2014.01.00003

MOJ

eISSN: 2373-4442

Immunology

Short Communication Volume 1 Issue 1

IL-10 Producing Regulatory B cells: Where Are We?

Armand Bensussan Bensussan,¹

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Adele de Masson,² Martine Bagot,³ Jean DavidBouaziz³

¹INSERM U, Hopital Saint Louis, France
²Laboratory of Onco-Dermatology, Immunology & Cutaneous Stem Cells, Paris Diderot University, France
³Department of Dermatology, Hopital Saint Louis, France

Correspondence: 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

Received: April 25, 2014 | Published: April 29, 2014

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

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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

Short Communication

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 disease⁸ 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⁺CD1d^hi phenotype (called “B10” cells) could diminish inflammation in mouse models of contact dermatitis,⁶ EAE¹² 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 CD24^highCD27⁺ B cell subset.^16,17 and CD24^highCD38^high 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 arthritis²⁰ 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.