Regulatory B cells play a key role in immune system balance

Regulatory B cells (Bregs) may act earlier than regulatory T cells (Tregs) and may play as important a role in autoimmune and allergic diseases. Obstacles to the investigation of Bregs are the same as those encountered for Tregs: the regulatory effects are short-lived in some cases, there is no consistent phenotype (C5 expression is neither indispensable nor sufficient), differences exist across species (e.g., between humans and mice), and there are a number of suppression modalities (IL-10, TGF-beta, expression of proapoptotic membrane molecules) that vary across Breg subtypes. The Breg subtypes may be homologous to the Treg subtypes (Br1 cells expressing IL-10, Br3 cells expressing TGF-beta, and B-Foxp3 cells), although the Br1 subtype seems to predominate. Nevertheless, differences with Treg cells may exist: Breg activation may chiefly involve the toll-like receptors rather than the antigen receptor; and Bregs act earlier, facilitating the recruitment of Tregs then disappearing once the Tregs become operational. Bregs make a major contribution to autoimmune disorders associated with several forms of immune deficiency, as well as to the absence of transplant rejection when there is a strong B cell response. Breg deficiencies have been reported in lupus, and the disappointing effects in this disease of treatments designed to inhibit the B cell response may be related to further Breg impairment. In several animal models, Breg stimulation is effective in correcting a variety of autoimmune disorders, most notably those initiated in the mucous membranes. Research into the interactions between the gut microbiota and Bregs holds considerable promise. (c) 2012 Societe francaise de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.