Journal
THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS
Volume 6, Issue 3, Pages 161-173Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/1756285612474333
Keywords
Multiple sclerosis; B cell; anti-CD20; experimental autoimmune encephalomyelitis; antibody; cellular subsets; intrathecal; immune phenotyping; therapy
Categories
Funding
- Else Kroner Fresenius Stiftung [A69/2010]
- Deutsche Forschungsgemeinschaft (DFG) [WE 3547/4-1]
- US National Multiple Sclerosis Society (NMSS) [PP 1660]
- ProFutura program of the University of Gottingen
- TEVA
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Recent years have substantially broadened our view on the pathogenesis of multiple sclerosis (MS). While earlier concepts focused predominantly on T lymphocytes as the key cell type to mediate inflammatory damage within central nervous system (CNS) lesions, emerging evidence suggests that B lymphocytes may play a comparably important role both as precursors of antibody-secreting plasma cells and as antigen-presenting cells (APCs) for the activation of T cells. With greater appreciation of this pathogenic B-cell function in MS, B-cell-directed therapies, and in particular B-cell-depleting monoclonal antibodies targeting the CD20 molecule, have gained enormous interest over recent years. Clinical trials demonstrated that anti-CD20 treatment, which depletes immature and mature B cells but spares CD20 negative plasma cells, rapidly reduces formation of new inflammatory CNS lesions. While these findings clearly corroborate a pathogenic contribution of B cells, recent experimental but also clinical findings indicate that not all B cells contribute in an equally pathogenic manner and that certain subsets may in contrast mediate anti-inflammatory effects. In this review, we summarize current findings in support of pathogenic B-cell function in MS, including the encouraging clinical data which derived from anti-CD20 MS trials. Further, we review novel findings suggestive of regulatory properties of B-cell subsets which may be collaterally abolished by pan-CD20 depletion. In conclusion, we aim to provide an outlook on how this currently differentiating concept of pro- and anti-inflammatory B-cell function could be harnessed to further improve safety and effectiveness of B-cell-directed therapeutic approaches in MS.
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