B cells and T cells are two major players in the pathogenesis of multiple sclerosis (MS) and cooperate at various check points. B cells, besides serving as a source for antibody-secreting plasma cells, are efficient antigen presenting cells for processing of intact myelin antigen and subsequent activation and pro-inflammatory differentiation of T cells. This notion is supported by the immediate clinical benefit of therapeutic B cell depletion in MS, presumably abrogating development of encephalitogenic T cells. However, different B cell subsets strongly vary in their respective effect on T cell differentiation which may relate to B cell phenotype, activation status, antigen specificity and the immunological environment where a B cell encounters a naïve T cell in. In this regard, some B cells also have anti-inflammatory properties producing regulatory cytokines and facilitating development and maintenance of other immunomodulatory immune cells, such as regulatory T cells. Reciprocally, differentiated T cells influence T cell polarizing B cell properties establishing a positive feedback loop of joint pro- or anti-inflammatory B and T cell developments. Further, under the control of activated T helper cells, antigen-primed B cells can switch immunoglobulin isotype, terminally commit to the plasma cell pathway or enter the germinal center reaction to memory B Cell development. Taken together, B cells and T cells thus closely support one another to participate in the pathogenesis of MS in an inflammatory but also in a regulatory manner.