Regulatory B Cells - Implications in Autoimmune and Allergic Disorders

Abstract

B lymphocytes are a major player in the immune system and their best understood effector functions are antibody production, presentation of antigens to T cells and modulation of immune responses via cytokine production. Most B cell functions are considered to amplify immune responses, but it has also been demonstrated that due to production of immunosuppressive cytokines or antibodies, B cells can down-regulate immune responses and have the ability to induce tolerance. These B cells with regulatory capacity (Breg cells) have been shown to suppress effector functions of various target cells including T cells, dendritic cells and macrophages, and can even convert effector T cells into regulatory T cells. The most prominent mechanism of Breg mediated suppression is the release of anti-inflammatory cytokines such as IL-10 and TGF-β. Additional suppression mechanisms via cell-cell contact, involving surface molecules such as program death-1 (PD-1), CD80/CD86 and FasL mediating target cell apoptosis, have been described as well. Most importantly, Breg cells have been implicated in various inflammatory conditions, such as allergic and autoimmune diseases. There is evidence for Breg deficiencies in human SLE patients and various adoptive transfer experiments in mouse models of autoimmune and allergic diseases indicate that Breg cells are capable of suppressing disease development. In this review we endeavour to give an overview of the current knowledge about regulatory B cell immunobiology and their implications in allergic and autoimmune conditions.