AGONISTIC AND ANTAGONISTIC EFFECTS OF CHOLERA-TOXIN ON HUMAN B-LYMPHOCYTE PROLIFERATION

Citation
P. Garrone et J. Banchereau, AGONISTIC AND ANTAGONISTIC EFFECTS OF CHOLERA-TOXIN ON HUMAN B-LYMPHOCYTE PROLIFERATION, Molecular immunology, 30(7), 1993, pp. 627-635
Citations number
39
Categorie Soggetti
Immunology,Biology
Journal title
ISSN journal
01615890
Volume
30
Issue
7
Year of publication
1993
Pages
627 - 635
Database
ISI
SICI code
0161-5890(1993)30:7<627:AAAEOC>2.0.ZU;2-T
Abstract
In our attempts to elucidate the mechanisms regulating the IL2- and IL 4-induced proliferation of human B lymphocytes, we studied the effects of cholera toxin (CT) and other agents increasing adenosine 3', 5'-cy clic monophosphate (cAMP) levels on tonsil B cells activated through t heir antigen receptors. CT enhanced proliferation of anti-IgM-costimul ated B cells in a dose-dependent fashion (1 ng/ml to 10 mug/ml), a pro perty shared in part by other agents inducing cAMP, such as forskolin, prostaglandin E2 and dibutyryl-cAMP, but not by the purified B subuni t of CT. However, when cytokine-dependent proliferation was studied, C T and cAMP-increasing agents inhibited IL2-induced DNA synthesis of an ti-IgM-activated B cells. This blockade was not due to a modification of the kinetics of proliferation, but was rather a consequence of part ial inhibition of IL2 receptor expression. In contrast CT and cAMP-ele vating agents enhanced the latest phases of the IL4-induced DNA synthe sis of anti-IgM-activated B cells. These results indicate that CT disp lays 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.