Journal
CURRENT OPINION IN IMMUNOLOGY
Volume 23, Issue 6, Pages 713-720Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.coi.2011.09.003
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Categories
Funding
- Pfizer Pharmaceuticals
- Bayer
- Bayhill Therapeutics
- Berlex
- Biogen-IDEC
- BioMS
- Diogenix
- Eli-Lilly
- Genentech
- GSK
- Guthy-Jackson/GGF
- Merck-Serono
- Novartis
- Ono Pharmacia
- Roche
- Sanofi Aventis
- Teva Neuroscience
- Wyeth
- EMD-Serono
- Teva Pharmaceuticals Inc./Teva Neuroscience
- Boehringer-Ingelheim, Inc.
- Bayhill Therapeutics, Inc.
- Genentech/Roche
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Over the past two decades B cells have increasingly moved into the spotlight in multiple sclerosis (MS) research. This interest was fuelled by growing understanding and acceptance of pathological involvement of B cells and antibodies in MS. Data derived from animal models of MS, human histopathological studies, and analyses of B cells in the peripheral blood and cerebrospinal fluid (CSF) have permitted the integration of B cells in our overall picture of MS immunopathogenesis. The as yet strongest direct evidence for a central role of B cells in MS autoimmunity was the demonstration that peripheral B cell depletion leads to a rapid decline of disease-activity in MS. While lending formidable impact to peripheral blood B cells as mediators of disease activity, the effects of anti-CD20 treatment also seemingly challenged the paradigm of a role of antibodies in targeted central nervous system (CNS) myelin destruction. This review shall attempt to provide an overview of our current understanding of B cell and antibody mediated mechanisms relevant to MS. We will include findings from, both, human studies, and animal models to highlight the complexity of B cell function as it pertains to MS. B cells appear to be effective drivers of inflammatory activity in MS by way of a diverse toolset of cellular functions. These functions appear to be closely linked to B cells that can be found in the periphery. However, by serving as the source of antibodies, B cells offer a direct humoral response that may target the CNS and lead to tissue specific destruction. Therefore, B cells participate in MS pathogenesis on both sides of the blood-brain barrier.
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