Molecular targeted therapy against B cells in multiple sclerosis

B cells have been implicated in the pathology of multiple sclerosis ( MS ) since the initial observation in the 1940s and 50s of increased immunoglobulin concentrations in the cerebrospinal fluid of MS patients. Until recently, B cells have been considered to participate in MS pathology through the secretion of antibodies specific to central nervous system antigens. However, the successful targeting of B cells with anti‐ CD 20 monoclonal antibodies without affecting immunoglobulin levels suggests that B cells have antibody‐independent functions in immune regulation in MS . Furthermore, the recent identification of B cell‐rich follicle‐like structures in the meninges of patients with secondary progressive MS indicates that B cells also have pathogenic roles within the central nervous system, where they contribute to disease progression by inducing cortical injury. These observations suggest that B cells are key players in the pathogenesis of MS , and are therefore attractive targets for therapeutic intervention. In addition to CD 20, several other molecules and pathways related to B cell function are being evaluated as therapeutic targets in other autoimmune diseases. Furthermore, based on the increased understanding of the molecular mechanisms underlying B cell effector function, particularly those involved in MS , therapeutic strategies for specifically inhibiting the pro‐inflammatory activity of B cells while preserving or even enhancing their role in protective immune response are under active investigation. Here, we review recent advances in molecular targeted therapies against B cells for MS , and discuss perspectives for future therapies targeting B cells and related molecules.