Agonistic and antagonistic effects of cholera toxin on human B lymphocyte proliferation.
In our attempts to elucidate the mechanisms regulating the IL2- and IL4-induced proliferation of human B lymphocytes, we studied the effects of cholera toxin (CT) and other agents increasing adenosine 3', 5'-cyclic monophosphate (cAMP) levels on tonsil B cells activated through their antigen receptors. CT enhanced proliferation of anti-IgM-costimulated B cells in a dose-dependent fashion (1 ng/ml to 10 micrograms/ml), a property shared in part by other agents inducing cAMP, such as forskolin, prostaglandin E2 and dibutyryl-cAMP, but not by the purified B subunit of CT. However, when cytokine-dependent proliferation was studied, CT and cAMP-increasing agents inhibited IL2-induced DNA synthesis of anti-IgM-activated B cells. This blockade was not due to a modification of the kinetics of proliferation, but was rather a consequence of partial inhibition of IL2 receptor expression. In contrast CT and cAMP-elevating agents enhanced the latest phases of the IL4-induced DNA synthesis of anti-IgM-activated B cells. These results indicate that CT displays agonistic and antagonistic effects on human B cell proliferation, most of these effects being reproduced by cAMP-elevating agents. Thus limited activation of the cAMP pathway in B cells may facilitate the development of TH2-type immune responses.
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
P
P
Garrone
J
J
Banchereau
D001402:B-Lymphocytes / Q000276:immunology*; D003994:Bucladesine / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D014066:Palatine Tonsil / Q000166:cytology; D015375:Receptors, Interleukin-2 / Q000378:metabolism
D007075:Immunoglobulin M; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D005576:Colforsin; D015847:Interleukin-4; D003994:Bucladesine; D002772:Cholera Toxin; D000242:Cyclic AMP; D015232:Dinoprostone