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.
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