• anti-CD20;
  • B cell;
  • B cell depletion;
  • multiple sclerosis;
  • plasmablast;
  • plasma cell


Until relatively recently, B cells were viewed as relatively passive recipients of T cell help, serving the primary normal function of protective antibody production. Similarly, their role in immune-mediated diseases, including multiple sclerosis (MS), was traditionally ascribed to production of pathogenic autoantibodies. However, new insights gained from both animal models and in humans, including studies of selective B cell targeting in patients, have shed light on non-antibody-mediated functions of B cells as immune regulators in both health and disease. Here, we consider the significance of the recent success of B cell depletion in patients with MS. We submit that it is no longer a question of whether B cells contribute to MS, but how B cells do so. In this review, we consider concepts of the different antibody-dependent and -independent biological roles that B cells might play in MS pathophysiology. Important data from the commonly used animal model of MS, experimental autoimmune encephalomyelitis (EAE), continues to contribute to our understanding of the molecular cascades involved in peripheral immune regulation and in immune-neural interactions that might be relevant to inflammatory events of multiple sclerosis. We focus this review on results from human-based studies, occasionally drawing on observations from animal models to highlight specific principles.