Amit Bar-Or, MD, FRCPC, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, shares the current understanding of the role of B-cells in the pathogenesis of multiple sclerosis (MS). The use of anti-CD20 therapies that selectively target B-cells in MS has shed light on their influence. While the role of central nervous system (CNS) antibodies in MS pathogenesis has long been recognized, there is a growing understanding of the non-antibody dependent functions of B-cells in this context. B-cells appear to be a valuable target in MS as evidence suggests that abnormal pro-inflammatory B-cells can overstimulate pro-inflammatory peripheral immune cells, leading to relapse upon CNS infiltration, as well as contribute to non-relapsing progressive disease when residing in the CNS. This interview took place during the ACTRIMS Forum 2021.