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J. Biol. Chem., Vol. 277, Issue 10, 7766-7775, March 8, 2002
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From the 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.
Distinct Role of CD80 and CD86 in the Regulation of the
Activation of B Cell and B Cell Lymphoma*
§,§,
, and**
Immunology Laboratory, Institute of
Microbial Technology, the Department of Experimental Medicine,
Postgraduate Institute of Medical Education & Research, Chandigarh
160036, and the ¶ Centre for DNA Fingerprinting and Diagnostics,
Hyderabad 500 076, India
*
This work was supported in part by the Council of Scientific
and Industrial Research, Government of India.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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