The role of B cells in the immunopathogenesis of multiple sclerosis

Abstract

There is ongoing debate on how B cells contribute to the pathogenesis of multiple sclerosis (MS). The success of B-cell targeting therapies in MS highlighted the role of B cells, particularly the antibody-independent functions of these cells such as antigen presentation to T cells and modulation of the function of T cells and myeloid cells by secreting pathogenic and/or protective cytokines in the central nervous system. Here, we discuss the role of different antibody-dependent and antibody-independent functions of B cells in MS disease activity and progression proposing new therapeutic strategies for the optimization of B-cell targeting treatments.

Keywords: B cells; B-cell-depleting therapies; antibodies; multiple sclerosis.

Figure 1

Different roles of B cells in the pathogenesis of multiple sclerosis. (a) B cells can differentiate into plasma cells and secrete autoantibodies that contribute to central nervous system (CNS) inflammation via opsonization of CNS antigens and complement fixation. (b) B cells can recognize and internalize the CNS antigens and act as antigen‐presenting cells (APCs) to activate CNS‐specific pathogenic T cells. (c) Different subsets of B cells in the CNS can modulate T‐cell and myeloid cell functions by secretion of pro‐inflammatory and anti‐inflammatory cytokines. B cells also produce interleukin‐6 (IL‐6) and present it in trans through their own IL‐6Rα, inducing Ly6G⁺ cell differentiation into polymorphonuclear myeloid‐derived suppressor cells (PMN‐MDSCs) and these MDSCs suppress B‐cell activation and cytokine production in a negative feedback loop.