Recent data underlines the direct role of B-cells in MS. Such comprehensive data have led to new therapeutic strategies using biotherapies in order to deplete, or modulate, the functions of peripheral B cells. Such approaches have led to contradictory results of efficacy. Today, it remains unclear whether B-cells exert diminished regulatory effects or instead potentiate the pathogenic response of T-cells. Such dual properties may depend on the release of inhibitory (e.g. interleukin-10) or pro-inflammatory cytokines (e.g. interleukin-6) and/or direct interactions with other cells, especially T cells.