Activation and proliferation signals in mouse B cells. VIII. Induction of DNA synthesis in B cells by a combination of calcium ionophores and phorbol myristate acetate.
Mouse B cells cultured with either phorbol myristate acetate (PMA), or with Ca2+ ionophores enter a transitional activated state, between quiescence (G0) and G1, but do not synthesize DNA. It is shown here that the combination of PMA plus the ionophore ionomycin induces resting B cells to synthesize DNA, but not to secrete antibody. B cells from CBA/N mice carrying the xid defect, and those from the lipopolysaccharide-unresponsive C3H/HeJ strain also respond to this combination. Suboptimal doses of the two stimuli synergize with B cell-stimulating factor 1 in promoting proliferation of resting B cells, but the co-mitogen does not substitute for type II B cell growth factor in the BCL1 lymphoma. Furthermore, (as predicted) the combination of these two agents does not induce the breakdown of inositol phospholipids in B cells. These data are consistent with the hypothesis that elevation of intracellular Ca2+ (by the ionophore), plus activation of protein kinase C (by PMA) leads to DNA synthesis in B cells. The combination of Ca2+ ionophore and PMA thus appears to essentially mimic the biochemical effects of ligation of surface immunoglobulin receptors on B cells, by providing the two second messengers normally emanating from the receptor-mediated breakdown of polyphosphoinositides.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000276:immunology*; D004247:DNA / Q000096:biosynthesis; D004357:Drug Synergism; D004987:Ethers / Q000008:administration & dosage; D005260:Female; D006133:Growth Substances / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D015847:Interleukin-4; D015759:Ionomycin; D008213:Lymphocyte Activation / Q000187:drug effects*; D008222:Lymphokines / Q000032:analysis; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010704:Phorbols / Q000008:administration & dosage*; D010716:Phosphatidylinositols / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage*
D004987:Ethers; D006133:Growth Substances; D000949:Histocompatibility Antigens Class II; D008222:Lymphokines; D010704:Phorbols; D010716:Phosphatidylinositols; D015847:Interleukin-4; D015759:Ionomycin; D004247:DNA; D013755:Tetradecanoylphorbol Acetate