cAMP-independent effects of cholera toxin on B cell activation. I. A possible role for cell surface ganglioside GM1 in B cell activation

• Published in: The Journal of immunology (1950) Vol. 145; no. 10; pp. 3162 - 3169
• Main Authors: Francis, ML, Moss, J, Fitz, TA, Mond, JJ
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.11.1990; American Association of Immunologists
• Subjects: 8-Bromo Cyclic Adenosine Monophosphate - pharmacology; Animals; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biological and medical sciences; Bucladesine - pharmacology; Cholera Toxin - pharmacology; Colforsin - pharmacology; Cyclic AMP - analysis; Cyclic AMP - physiology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; G(M1) Ganglioside - physiology; Immunobiology; Lymphocyte Activation - drug effects; Mice; Mice, Inbred DBA; Modulation of the immune response (stimulation, suppression); Rodentia; Cyclic AMP; Molecular interaction; Activation; B-Lymphocyte; Cell surface; Infection; Toxin; Vertebrata; Membrane receptor; Mammalia; Ganglioside; Mouse; Bacteriosis; Cholera
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.145.10.3162

Cholera toxin has been used as a tool to study the effects of cAMP on the activation of B cells but may have effects independent of its ability to elevate cAMP. We found five lines of evidence which suggested that cholera toxin suppressed mitogen-stimulated B cell activation through a cAMP-independent pathway. 1) Cholera toxin (1 microgram/ml) was consistently more suppressive than forskolin (100 microM) despite the induction of higher intracellular cAMP levels by forskolin. 2) Cholera toxin was more suppressive at 1 microgram/ml than at 0.1 microgram/ml despite equivalent elevations of cAMP. 3) Washing B cells following their incubation with cholera toxin reversed much of the inhibition without altering intracellular cAMP levels. 4) The A subunit of cholera toxin, which at high concentrations (10 micrograms/ml) induced levels of cAMP comparable to those induced by cholera toxin (1 and 0.1 microgram/ml), did not inhibit B cell activation. 5) cAMP derivatives at high concentrations were much less effective than was cholera toxin in suppressing B cell activation. Although the elevation of cAMP may cause a mild inhibition of B cell proliferation, we found that even a marked elevation of cAMP did not suppress B cell proliferation, unless the elevation was persistent. We did, however, observe that the degree of toxin inhibition more closely paralleled binding of the toxin to B cells than toxin stimulation of cAMP. This result raised the possibility that binding of cholera toxin to its ganglioside GM1 receptor mediated an inhibitory signal which suppressed B cell proliferation.