Strategies for treating autoimmune disorders are increasingly employing targeted 
therapies rather than non-specific, multitargeted treatments. Accumulating 
evidence on the involvement of B lymphocytes in the pathophysiology of 
autoimmune demyelinating disease has led to a renewed interest in B cells as 
potential therapeutic targets. In particular, antigen presentation between B 
cells and T cells, increased trafficking of B cells across the blood-brain 
barrier, and autoantibodies produced by plasma cells may contribute to the 
pathophysiology of autoimmune disorders such as multiple sclerosis. Several 
B-cell-targeted, depletion therapies are currently in development, including 
rituximab, epratuzumab, diphtheria toxin-single chain Fv (DC2219), belimumab, 
atacicept, abatacept, and abetimus sodium. Of these agents, only rituximab and 
abatacept have been evaluated in multiple sclerosis patients. Preliminary 
results of a phase II trial of rituximab in multiple sclerosis suggest that 
rituximab is well tolerated and significantly reduces the number of gadolinium 
enhancing lesions over 24 weeks of treatment. Results of an exploratory analysis 
suggest the potential promise of abatacept 10 mg/kg for multiple sclerosis. It 
is expected that future clinical trials will establish a role for 
B-cell-targeted therapies in the treatment of multiple sclerosis and other 
autoimmune neurological diseases. This article describes the mechanism of action 
behind B-cell-targeted depletion therapies in development and reviews available 
clinical data.