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Secretory products of multiple sclerosis B cells are cytotoxic to oligodendroglia in vitro.
MedLine Citation:
PMID:  22458983     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
B cells are important in the pathogenesis of multiple sclerosis (MS) and some of the effects are not dependent on maturation of B cells into immunoglobulin (Ig) producing plasmablasts and plasma cells. B cells present antigen, activate T cells, and are involved in immunoregulation and cytokine secretion. To determine if B cells from MS patients secrete products that have deleterious effects on glial cells not mediated by Ig, and to compare effects with secretory products of normal controls (NC), we isolated B cells from 7 patients with relapsing remitting MS (RRMS) and 4 NC. B cells were cultured alone or after stimulation with CD40 ligand (CD40L), CD40L+cross-linking of the B cell antigen receptor (xBCR) and CD40L+xBCR+stimulation of toll like receptor 9 (TLR9). Supernatants were harvested and incubated with mixed central nervous system (CNS) neonatal rat glial cells. Supernatants from unstimulated NC B cells induced on average death of 7% (range 0-24%) of differentiated oligodendrocytes (OL); in contrast, supernatants from unstimulated B cells from RRMS patients induced death of 57% (range 35-74%) of OL. Supernatants of stimulated B cells from NC did not increase the minimal OL death whereas stimulation of B cells from RRMS had variable results compared to unstimulated B cells. Supernatants from both NC and RRMS induced microglial enlargement and loss of normal resting bipolar morphology. OL death did not correlate with levels of tumor necrosis alpha (TNF-α), lymphotoxin alpha (LT-α), interleukin 6 (IL-6), IL-10, transforming growth factor beta 1 (TGF-β1) or any combination or ratio of these cytokines. Analysis of 26 supernatants from NC and RRMS patients failed to detect IgM. There were very low levels of IgG in 8 of the 26 supernatants, and no correlation between of OL death and presence or absence of IgG. Sera used in both the B cell and glial cell cultures were heated, which inactivates complement. The effects of B cell supernatants on OL could be direct and/or indirect involving either microglia and/or astrocytes. The identity of the toxic factor(s) is as yet unknown. Thus we have demonstrated that B cells from patients with RRMS but not NC secrete one or more factors toxic to OL. It is possible that such factors produced by peripheral blood B cells when within the CNS could contribute to demyelination in MS patients.
Authors:
Robert P Lisak; Joyce A Benjamins; Liljana Nedelkoska; Jennifer L Barger; Samia Ragheb; Boli Fan; Nadia Ouamara; Trina A Johnson; Sathyanath Rajasekharan; Amit Bar-Or
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-28
Journal Detail:
Title:  Journal of neuroimmunology     Volume:  -     ISSN:  1872-8421     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8109498     Medline TA:  J Neuroimmunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
Affiliation:
Department of Neurology, Wayne State University, Detroit MI 48201 USA; Department of Immunology and Microbiology, Wayne State University, Detroit MI 48201 USA.
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