The T-lymphocyte is the primary cellular target for potentiation of the in vitro T-dependent IgM antibody response by the B subunit of cholera toxin.
The B (or binding) subunit of cholera toxin (CTB) was reported previously to potentiate the in vitro T-dependent IgM antibody response by a mechanism independent of the cyclic AMP-generating capacity of the intact toxin. In the present report, experiments were designed to determine the immune cell type mediating potentiation by CTB. Firstly, CTB did not potentiate T-independent antibody responses at concentrations that effectively enhanced T-dependent responses. Secondly, separation/reconstitution studies with splenocytes from CTB- and vehicle-treated mice demonstrated potentiation of T-dependent responses by CTB treatment of either the Sephadex G10 non-adherent population or the T-lymphocyte + macrophage population of cells. Potentiation was not observed by CTB treatment of the plastic adherent population or the B-lymphocyte + macrophage population. The evidence indicates that the T-lymphocyte is the primary cellular target for CTB-induced effects on the T-dependent IgM antibody response. Monosialoganglioside GM1, the putative binding site for CTB, is most likely the site of action for CTB on T-lymphocytes. These studies provide new insight on the mechanism of immunomodulation by cholera toxin, and CTB should provide a useful tool for further understanding the role of gangliosides in cellular immune responses.
Campbell
K S
KS
Medical College of Virginia/Virginia Commonwealth University, Department of Pharmacology and Toxicology, Richmond 23298.
Fuchs
B A
BA
Munson
A E
AE
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology*; D005260:Female; D007075:Immunoglobulin M / Q000096:biosynthesis*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D000276:Adjuvants, Immunologic; D000955:Antigens, T-Independent; D007075:Immunoglobulin M; D010446:Peptide Fragments; C050310:cholera toxin, B subunit (50-64); D002772:Cholera Toxin