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The Journal of Immunology, Vol 145, Issue 8 2375-2380, Copyright © 1990 by American Association of Immunologists
ARTICLES |
ED Anastassiou, H Yamada, ML Francis, JJ Mond and GC Tsokos
Kidney Diseases Section, National Institute of Diabetes Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD 20892.
Experiments were performed to investigate the effect of cholera toxin (CT) on human B cell function. Highly purified (greater than 98% CD20+) human peripheral blood B cells were exposed to CT in the presence or absence of anti-mu antibody. Treatment of highly purified B cells with CT stimulated enhanced expression of surface DR molecules, whereas it did not enhance expression of other B cell surface activation markers including transferrin or IL-2R. Neither the A nor the B subunits of CT by themselves enhanced the expression of surface DR Ag. In addition, 8- bromo-cAMP alone or in combination with the B subunit did not increase the expression of human B cell surface DR Ag. These findings suggest that neither elevation of cAMP nor binding to GM1 ganglioside are sufficient to stimulate this activation parameter in B cells. Associated with CT-mediated enhanced expression of MHC class II molecules we found that CT-treated B cells also served as stronger stimulators, compared with control cells, of both autologous and allogeneic MLR responses in peripheral blood T cells. Although CT stimulated early events in B cell activation, it inhibited anti-mu antibody-induced B cell thymidine incorporation by 55 to 75%. Inhibitory effects of CT were observed even when CT was added to cultures as late as 36 h after the addition of the anti-mu antibody. These results suggest that CT has both a stimulatory and inhibitory effect on human B cells and that the stimulatory effect may be mediated via a cAMP-independent mechanism.
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