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
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.