Early events in human B cell activation: metabolic pathways vary according to the first signal used.
The effects of the calcium channel blocking drug Verapamil and of palmitoyl-carnitine (PTC), an inhibitor of protein-kinase C activity, on human B cell activation were measured. Both Verapamil and PTC inhibited the B cell proliferation induced by costimulation with anti-mu antibody and with 3 different growth factors: interleukin 2, 20-kDa B cell growth factor and 50-kDa B cell growth factor. Both uridine and thymidine incorporation induced by costimulation with ionomycin and phorbol 12-myristate 13-acetate (PMA) were inhibited by Verapamil and PTC. In contrast, B cell proliferation was resistant to Verapamil (while being still inhibited by PTC) in two situations: when B cells were costimulated with PMA and growth factors and when B cells previously activated in vitro (by anti-mu antibody or PMA) were stimulated with growth factors. These results confirm that the late stage (G1----S transition) of B cell activation is independent of Ca2+ entry. More importantly, they show that the initial events induced by anti-mu antibody and by PMA are based on different biochemical pathways: PMA would act on a subpopulation of B cells which has already received an early signal of activation in vivo. This emphasizes the functional and biochemical heterogeneity of the G0 stage among circulating B cells.
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000502:physiology*; D002453:Cell Cycle; D002472:Cell Transformation, Viral; D004247:DNA / Q000096:biosynthesis; D004987:Ethers / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D004854:Herpesvirus 4, Human; D006801:Humans; D015847:Interleukin-4; D015759:Ionomycin; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology; D010172:Palmitoylcarnitine / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D004987:Ethers; D006133:Growth Substances; D008222:Lymphokines; D010172:Palmitoylcarnitine; D015847:Interleukin-4; D015759:Ionomycin; D004247:DNA; D014700:Verapamil; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium