For decades, B cells were ignored in multiple sclerosis (MS) pathogenesis, and 
the disease was always regarded as a T cell-mediated disorder. Recent evidence 
shows that there is an antigen-driven B-cell response in the central nervous 
system of patients with MS, and memory B cells/plasma cells are detectable in MS 
lesions. The striking efficacy of B cell-depleting therapies in reducing the 
inflammatory activity of the disease highlights that B cells may play more 
pathogenetic roles than expected. B cells express several unique characteristic 
markers on their surface, for example, CD19, CD20 molecules, that provide 
selective targets for monoclonal antibodies. In this respect, several B 
cell-targeted therapies emerged, including anti-CD20 antibodies (rituximab, 
ocrelizumab, and ofatumumab), anti-CD19 antibody (inebilizumab), and agents 
targeting the BAFF/APRIL signaling pathway (atacicept, belimumab, and 
LY2127399). In this review, we discuss, in detail, the immunobiology of B cells 
and their protective and destructive roles in MS pathogenesis. In the second 
part, we list the completed and ongoing clinical trials investigating the safety 
and efficacy of B cell-related monoclonal antibodies in MS.