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Abstract
Understanding the pathogenesis of complex immunologic disorders such as multiple sclerosis (MS) is challenging. Abnormalities in many different cell types are observed in the immune system and CNS of patients with MS and the identification of the primary and secondary events is difficult. Recent studies suggest that the model of MS as a disorder mediated only by T cells is overly simplistic and propose an important role for B cells in the propagation of the disease. B-cell activation in the form of oligoclonal bands (OCB) production is the most consistent immunologic finding in patients with MS. Notably, markers of B-cell activation within the CSF of patients with MS predict conversion from clinically isolated syndrome to clinically definite MS and correlate with MRI activity, onset of relapses, and disability progression. In addition, the main genetic risk factor in MS is associated with OCB production, and environmental agents associated with MS susceptibility (vitamin D and the Epstein-Barr virus) influence B-cell proliferation and function. Finally, the only cell-specific treatments that are effective in patients with MS are monoclonal antibodies targeting the B-cell antigen CD20, suggesting a potentially causative role for B cells. Based on current evidence there is no longer doubt that B cells are relevant to the etiology and pathogenesis of MS. Elucidating the role of B cells in MS will be a fruitful strategy for disease prevention and treatment.
GLOSSARY
- CDMS=
- clinically definite multiple sclerosis;
- ChIP-seq=
- chromatin immunoprecipitation followed by massively parallel DNA sequencing;
- CIS=
- clinically isolated syndrome;
- EAE=
- experimental autoimmune encephalomyelitis;
- EBNA=
- Epstein-Barr nuclear antigen;
- EBV=
- Epstein-Barr virus;
- GC=
- germinal center;
- IL=
- interleukin;
- IM=
- infectious mononucleosis;
- LCL=
- lymphoblastoid cell line;
- LMP=
- latent membrane protein;
- MBP=
- myelin basic protein;
- MHC=
- major histocompatibility complex;
- MOG=
- myelin oligodendrocyte glycoprotein;
- MS=
- multiple sclerosis;
- OCB=
- oligoclonal bands;
- PLP=
- proteolipid protein;
- PPMS=
- primary progressive multiple sclerosis;
- RRMS=
- relapsing-remitting multiple sclerosis;
- SPMS=
- secondary progressive multiple sclerosis;
- Th=
- T helper cells;
- VDR=
- vitamin D receptor;
- VDRE=
- vitamin D responsive element
Footnotes
Study funding: Supported by the Wellcome Trust (075491/Z/04) and by a research fellowship FISM Fondazione Italiana Sclerosi Multipla-Cod.: 2010/B/5.
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Supplemental data at www.neurology.org
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References e1–e45 are available on the Neurology® Web site at www.neurology.org.
- Received August 8, 2011.
- Accepted October 17, 2011.
- Copyright © 2012 by AAN Enterprises, Inc.
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