Suppressive functions of activated B cells in autoimmune diseases reveal the dual roles of Toll‐like receptors in immunity

<jats:p><jats:bold>Summary: </jats:bold> B lymphocytes contribute to immunity through production of antibodies, antigen presentation to T cells, and secretion of cytokines. B cells are generally considered in autoimmune diseases as drivers of pathogenesis. This view is certainly justified, given the successful utilization of the B cell‐depleting reagent rituximab in patients with rheumatoid arthritis or other autoimmune pathologies. In a number of cases, however, the depletion of B cells led to an exacerbation of symptoms in patients with autoimmune disorders. In a similar manner, mice lacking B cells can develop an aggravated course of disease in several autoimmune models. These paradoxical observations are now explained by the concept that activated B cells can suppress immune responses through the production of cytokines, especially interleukin‐10. Here, we review the stimulatory signals that induce interleukin‐10 secretion and suppressive functions in B cells and the phenotype of the B cells with such characteristics. Finally, we formulate a model explaining how this process of immune regulation by activated B cells can confer advantageous properties to the immune system in its combat with pathogens. Altogether, this review proposes that B‐cell‐mediated regulation is a fundamental property of the immune system, with features of great interest for the development of new cell‐based therapies for autoimmune diseases.</jats:p>