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Distinct role of CD80 and CD86 in the regulation of the activation of B cell and B cell lymphoma.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Distinct role of CD80 and CD86 in the regulation of the activation of B cell and B cell lymphoma.
 
Creator Suvas, Susmit
Singh, Vinod
Sahdev, Sudhir
Vohra, H
Agrewala, J N
 
Subject QD Chemistry
 
Description To date, not much has been known regarding the role of CD80 and CD86 molecules in signaling of B cells. The CD28/CTLA4 ligands, CD80 (B7-1) and CD86 (B7-2), are expressed on the surface of freshly isolated splenic B cells, and their expression is up-regulated by lipopolysaccharides. In the present study, we have investigated whether signaling via CD80/CD86 could alter the proliferation and immunoglobulin synthesis of B cells. Splenic B cells were stimulated with lipopolysaccharides in the presence of anti-B7-1 (16-10A1) and anti-B7-2 (GL1) monoclonal antibodies (mAbs). Exciting features observed during the study were that cross-linking of CD86 with GL1 enhanced the proliferation and production of IgG1 and IgG2a isotypes. In contrast, anti-B7-1 (16-10A1) mAb could efficiently block the proliferation and production of IgG1 and IgG2a. Furthermore, GL1 mAb could also induce the secretion of IgG isotypes from B cell lymphomas. Importantly, 16-10A1 could retard the growth of lymphomas and favored the up-regulation of pro-apoptotic molecules caspase-3, caspase-8, Fas, FasL, Bak, and Bax and down-regulation of anti-apoptotic molecule Bcl-x(L). In contrast, GL1 augmented the level of anti-apoptotic molecules Bcl-w and Bcl-x(L) and decreased the levels of pro-apoptotic molecule caspase-8, thereby providing a novel insight into the mechanism whereby triggering through CD80 and CD86 could deliver regulatory signals. Thus, this study is the first demonstration of a distinct signaling event induced by CD80 and CD86 molecules in B cell lymphoma. Finally, the significance of the finding is that CD80 provided negative signal for the proliferation and IgG secretion of normal B cells and B cell lymphomas. In contrast, CD86 encouraged the activity of B cells.
 
Publisher ASBMB
 
Date 2002-03-08
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/281/1/agrewala2002.pdf
Suvas, Susmit and Singh, Vinod and Sahdev, Sudhir and Vohra, H and Agrewala, J N (2002) Distinct role of CD80 and CD86 in the regulation of the activation of B cell and B cell lymphoma. The Journal of biological chemistry, 277 (10). pp. 7766-75. ISSN 0021-9258
 
Relation http://www.jbc.org/content/277/10/7766.long
http://crdd.osdd.net/open/281/