Regulatory functions of B cells in allergic diseases

Abstract

B cells are essentially described for their capacity to produce antibodies ensuring anti-infectious immunity or deleterious responses in the case of autoimmunity or allergy. However, abundant data described their ability to restrain inflammation by diverse mechanisms. In allergy, some regulatory B-cell subsets producing IL-10 have been recently described as potent suppressive cells able to restrain inflammatory responses both in vitro and in vivo by regulatory T-cell differentiation or directly inhibiting T-cell-mediated inflammation. A specific deficit in regulatory B cells participates to more severe allergic inflammation. Induction of allergen tolerance through specific immunotherapy induces a specific expansion of these cells supporting their role in establishment of allergen tolerance. However, the regulatory functions carried out by B cells are not exclusively IL-10 dependent. Indeed, other regulatory mechanisms mediated by B cells are (i) the production of TGF-b, (ii) the promotion of T-cell apoptosis by Fas-Fas ligand or granzyme-B pathways, and (iii) their capacity to produce inhibitory IgG4 and sialylated IgG able to mediate anti-inflammatory mechanisms. This points to Bregs as interesting targets for the development of new therapies to induce allergen tolerance. In this review, we highlight advances in the study of regulatory mechanisms mediated by B cells and outline what is known about their phenotype as well as their suppressive role in allergy from studies in both mice and humans.Allergic diseases encompass many heterogeneous pathologies with distinct clinical manifestations. These pathologies generally result from an uncontrolled inflammatory response to allergens and can lead to a number of disorders, including asthma, allergic rhinoconjunctivitis, anaphylaxis, urticaria, and atopic dermatitis. Mechanisms promoting allergic inflammation in mucosal tissues are characterized by dysregulated type 2 immunity with a dramatic T H 2-driven immunity, elevated allergen-specific IgE, leading to goblet cell hyperplasia and mucus overproduction. One significant cause of the development and persistence of allergic inflammation is an alteration in the immune regulatory processes (1). Regulatory T cells have long been the focus of all attention in the maintenance of allergen tolerance (2, 3), but recently, a new subset of B cells has been identified as regulatory (Bregs), due to their capacity to secrete IL-10 and constrain severe inflammation (4). In humans, B-cell depletion was recently suggested to exacerbate ulcerative colitis, promote psoriasis, or aggravate inflammation in patients with multiple sclerosis (5-7). These observations demonstrated the role of Bregs in the control of T-cell-mediated inflammation in vivo. Bregs cells are of special interest in allergic diseases also, as demonstrated by recent reports showing their potential implication in the development of allergen tolerance (8-10). However, the regulatory functions carried out by B cells are not exclusively IL-10 dependent. Indeed, ...

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