B cells with regulatory properties in transplantation tolerance

Abstract

Induction of tolerance remains a major goal in transplantation. Indeed, despite potent immunosuppression, chronic rejection is still a real problem in transplantation. The humoral response is an important mediator of chronic rejection, and numerous strategies have been developed to target either B cells or plasma cells. However, the use of anti-CD20 therapy has highlighted the beneficial role of subpopulation of B cells, termed regulatory B cells. These cells have been characterized mainly in mice models of auto-immune diseases but emerging literature suggests their role in graft tolerance in transplantation. Regulatory B cells seem to be induced following inflammation to restrain excessive response. Different phenotypes of regulatory B cells have been described and are functional at various differentiation steps from immature to plasma cells. These cells act by multiple mechanisms such as secretion of immuno-suppressive cytokines interleukin-10 (IL-10) or IL-35, cytotoxicity, expression of inhibitory receptors or by secretion of non-inflammatory antibodies. Better characterization of the development, phenotype and mode of action of these cells seems urgent to develop novel approaches to manipulate the different B cell subsets and the response to the graft in a clinical setting.

Keywords: Antibodies; Immuno-suppressive cytokines interleukin-10; Regulatory B cells; Suppression; Tolerance.

Figure 1

Different subpopulations and mechanisms described for regulatory B cells according to the literature. NK: Natural killer; MZP: Marginal zone precursor; APC: Antigen presenting cells; EC: Endothelial cells; IL: Interleukin; PD-L: Programmed death receptor ligand; TRAIL: Tumor necrosis factor-related apoptosis inducing-ligand; FasL: Fas ligand.