Activation and proliferation signals in mouse B cells. VII. Calcium ionophores are non-mitogenic polyclonal B-cell activators.
Calcium ionophores cause polyclonal proliferation of lymphocytes from man, rabbit and pig, but are not mitogenic for mouse T or B lymphocytes. We show here that two Ca2+ ionophores (A23187 and ionomycin) nonetheless activate a substantial proportion of mouse B lymphocytes at concentrations which effectively inhibit DNA synthesis induced by conventional mitogens, such as anti-immunoglobulin antibodies. Activation of B cells was detected by (i) increased expression of Ia antigen after 24 hr culture with ionophores, and (ii) the accelerated onset of DNA synthesis in B cells primed with ionophores for 24 hr, washed and then rechallenged with anti-Ig. Unlike anti-Ig, the ionophores did not induce either the breakdown of inositol phospholipids, or RNA synthesis in B cells. Finally, activation of B cells by ionophores is highly susceptible to inhibition by cyclosporine. These results therefore suggest that elevation of intracellular Ca2+ induced by these ionophores is sufficient to cause B cells to leave Go, but not to enter the G1 phase of the cell cycle. Clearly, additional signals are required for B cells to progress further into cycle and eventually become committed to DNA synthesis.
Klaus
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Bijsterbosch
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Holman
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D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D015759:Ionomycin; D007476:Ionophores / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008938:Mitosis / Q000187:drug effects; D010716:Phosphatidylinositols / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis
D004987:Ethers; D000949:Histocompatibility Antigens Class II; D007476:Ionophores; D010716:Phosphatidylinositols; D000001:Calcimycin; D015759:Ionomycin; D012313:RNA; D004247:DNA