Cholera toxin promotes the proliferation of anti-mu antibody-prestimulated human B cells.
The predominant effect of cholera toxin (CT) on cell growth has been postulated to be inhibitory as a result of its induction of intracellular cAMP. We have recently reported that CT selectively enhances surface DR expression while it inhibits anti-mu antibody-induced B lymphocyte proliferation. In the present series of experiments we studied the effect of CT on in vitro preactivated highly purified (greater than 95% CD20+) human B cells. Cholera toxin enhanced thymidine incorporation of anti-mu antibody-preactivated but not of Staphylococcus aureus Cowan I or PMA + ionomycin-preactivated B cells. Concentrations of 100 pg/ml CT stimulated an enhancement of thymidine incorporation equivalent to that of optimal doses of BCGF. The growth factor-like effect of CT required the complete molecule, since binding of purified B subunit (B-CT) to GM1 ganglioside by itself did not reproduce the holotoxin effect. Moreover, B-CT pretreatment of anti-mu antibody-primed cells completely neutralized the holotoxin-enhancing effect. Both PGE2, a physiological agent that stimulates intracellular cAMP elevation, and the cAMP analogue, 8-bromo-cAMP, mimicked the growth-promoting effect of CT. However, the ED50 of CT required to augment proliferation in anti-mu antibody-preactivated human B cells was approximately 100 times less than the ED50 for cAMP formation. These results demonstrate a specific growth factor-like promoting effect of CT on sIg-preactivated highly purified human B cells that may be mediated at least in part through elevation in intracellular cAMP levels. Increased DR expression and stimulation of growth of sIg preactivated B cells may explain some of the adjuvant properties of CT following orally or parenterally administered antigens.
Anastassiou
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ED
Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
Yamada
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H
Boumpas
D T
DT
Tsokos
G C
GC
Thyphronitis
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G
Balow
J
J
Mond
J J
JJ
D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000276:immunology; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015847:Interleukin-4; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin; D002772:Cholera Toxin; D000242:Cyclic AMP