Deciphering the Role of B Cells in Multiple Sclerosis—Towards Specific Targeting of Pathogenic Function

• Main Authors: Klaus Lehmann-Horn, Silke Kinzel, Martin S. Weber
• Format: Article
• Language: English
• Published: MDPI AG 2017-09-01
• Series: International Journal of Molecular Sciences
• Subjects: multiple sclerosis; B cells; antibodies; antigen presenting cells; anti-CD20; plasma cells; B cell therapies; experimental autoimmune encephalomyelitis; regulatory B cells
• Online Access: https://www.mdpi.com/1422-0067/18/10/2048

B cells, plasma cells and antibodies may play a key role in the pathogenesis of multiple sclerosis (MS). This notion is supported by various immunological changes observed in MS patients, such as activation and pro-inflammatory differentiation of peripheral blood B cells, the persistence of clonally expanded plasma cells producing immunoglobulins in the cerebrospinal fluid, as well as the composition of inflammatory central nervous system lesions frequently containing co-localizing antibody depositions and activated complement. In recent years, the perception of a respective pathophysiological B cell involvement was vividly promoted by the empirical success of anti-CD20-mediated B cell depletion in clinical trials; based on these findings, the first monoclonal anti-CD20 antibody—ocrelizumab—is currently in the process of being approved for treatment of MS. In this review, we summarize the current knowledge on the role of B cells, plasma cells and antibodies in MS and elucidate how approved and future treatments, first and foremost anti-CD20 antibodies, therapeutically modify these B cell components. We will furthermore describe regulatory functions of B cells in MS and discuss how the evolving knowledge of these therapeutically desirable B cell properties can be harnessed to improve future safety and efficacy of B cell-directed therapy in MS.