Regulatory B cells: Phenotype, function and role in transplantation

•While many B cell subsets have been associated with regulatory capacity, no definitive marker of Bregs exist.•Various mechanisms of action have been described for Bregs, such as the production of IL-10, IL-35 and TGFβ. Contact-mediated suppression of immune responses have been described as well.•In murine models of transplantation, several subsets of Bregs have been shown to be capable of suppressing alloimmune responses.•Recently, it has been found that the tolerance fingerprint in renal transplant recipients is confounded by the lack of immunosuppressive drugs.

While B cells are traditionally known for their roles in antibody production, antigen presentation and cytokine production, recent studies have highlighted the existence of B cells with regulatory properties, which have been termed Bregs, analogous to regulatory T cells (Tregs). Bregs have been found to play a role in autoimmune disease, malignancies, infections, and may also be involved in solid organ transplantation. Their main mechanism of action is by promoting the development of Tregs while suppressing effector CD4+ and CD8+ T cells, primarily by IL-10 secretion. In the field of transplantation evidence for an active role of Bregs is scarce. While the presence of Bregs has been associated with improved graft survival and operational tolerance in kidney transplant recipients, these findings are not without controversy. Since the majority of fundamental research on Bregs has been performed in the fields in autoimmunity and infectious diseases, we will first focus on what these fields taught us on basic Breg biology, after which the relevance for the transplant setting is discussed.