Cyclic AMP-independent effects of cholera toxin on B cell activation. II. Binding of ganglioside GM1 induces B cell activation.
Although the physiologic function of gangliosides is unknown, evidence suggests they play a role in the regulation of cell growth. The binding of ganglioside GM1 by recombinant B subunit of cholera toxin (rCT-B) inhibited mitogen-stimulated B cell proliferation without elevating intracellular cAMP. CT-B paradoxically enhanced the expression of MHC class II (Ia) molecules and minor lymphocyte-stimulating determinants without altering the expression of some other immunologically relevant B cell surface Ag. Increased expression of Ia was not detected until 4 h after stimulation, kinetics similar to those seen when B cells are stimulated with anti-Ig antibody or IL-4, suggesting that the enhancement was not the result of redistribution of existing cell surface markers but rather the result of a new metabolic event. Both the inhibitory and stimulatory effects of CT-B could be blocked by incubation of CT-B with ganglioside GM1. Furthermore, enhancement of the CT-B-mediated effect was seen when additional ganglioside GM1 was incorporated into the B cell membrane. rCT-B with a mutation that interfered with its binding to ganglioside GM1 did not enhance Ia expression. Taken together, these results indicate that the observed effects of CT-B were most likely mediated through the binding of cell surface ganglioside GM1. CT-B-mediated stimulation of Ia expression provides a potential explanation for the previously described ability of CT-B to act as an immunoadjuvant. These results suggest that the binding of ganglioside GM1 has multiple B cell growth-regulating effects.
Francis
M L
ML
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
Ryan
J
J
Jobling
M G
MG
Holmes
R K
RK
Moss
J
J
Mond
J J
JJ
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002772:Cholera Toxin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology*; D005260:Female; D005677:G(M1) Ganglioside / Q000378:metabolism* / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016747:Minor Lymphocyte Stimulatory Antigens / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D016747:Minor Lymphocyte Stimulatory Antigens; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; D000242:Cyclic AMP