Inhibition of calcium-dependent pathways of B-cell activation by DMBA.
The purpose of the experiments described in these studies was to determine the effects of 7,12-dimethylbenz[a]anthracene (DMBA) on B-cell activation produced by anti-IgD antibodies and interleukin-4 (IL-4). B and T cells are known to share many of the same biochemical pathways for cell activation by mitogen and antigen receptors. Previous studies in this laboratory have shown that DMBA inhibits mitogen-induced Ca2+ mobilization in murine and human T cells and produces an increase in intracellular Ca2+ in resting cells. The results of the present studies demonstrate that DMBA increases Ca2+ in resting B cells and inhibits B cell activation produced by anti-IgD antibodies, as measured by mobilization of free intracellular Ca2+ and [3H]thymidine incorporation. The proliferative response of B cells to insolubilized anti-IgD was suppressed only when cells were preexposed to DMBA. In contrast, IL-4 pathways of B-cell activation were insensitive to inhibition by DMBA, even when cells were preexposed. The induction of Class II MHC antigen (Ia) antigens on B cells by IL-4 was also found to be insensitive to DMBA treatment. These results suggest that DMBA suppresses only Ca(2+)-dependent pathways of B cell activation and indicate that altered Ca2+ homeostasis may be responsible for immunosuppression induced by this agent.
Davis
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DA
University of New Mexico, College of Pharmacy Toxicology Program, Albuquerque 87131.
Burchiel
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SW
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007072:Immunoglobulin D / Q000276:immunology; D015847:Interleukin-4 / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013268:Stimulation, Chemical
D000888:Antibodies, Anti-Idiotypic; D000949:Histocompatibility Antigens Class II; D007072:Immunoglobulin D; C039951:anti-IgD; D015847:Interleukin-4; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D002118:Calcium