Regulation of B cell activation by prostaglandins: cell cycle-specific effects on activation by anti-immunoglobulin and 8-mercaptoguanosine.
The current studies were undertaken to explore the regulatory effects of macrophages and their soluble products on B cell activation in defined medium by surface membrane-directed mitogens (anti-Ig, LPS) and by intracellular mitogens (8-mercaptoguanosine, [8MGuo]). Supplementation of macrophage-depleted B cell cultures with adherent cells enhanced the response to anti-Ig but depressed the response to 8MGuo. These changes could be eliminated by adding indomethacin to B cell cultures containing supplemental macrophages. Moreover, they could be reproduced by adding exogenous prostaglandins (PGE1, PGE2) but not other macrophage products to cultured B cells. Prostaglandins regulate B cell function (i.e., immunoglobulin secretion) in the same manner as they do mitogenesis. Thus, the polyclonal response to LPS is enhanced, whereas that to 8MGuo is inhibited. We showed previously that anti-Ig acts on a B cell subpopulation distinct from that stimulated by 8MGuo. Moreover, when addition of prostaglandin is delayed for more than 24 hr, the effect on the anti-Ig response changes from enhancement to inhibition and the effect on 8MGuo is lost, suggesting that in the course of activation the cell progresses through a series of cell cycle-specific regulatory states. Additionally, the mitogenic effects of 8MGuo appear to involve larger, cycling cells more than smaller cells. In concert, these data suggest a model for regulation of the B cell cycle in which prostaglandins, whose secretion is elicited by many surface-directed B cell stimuli, enhance the entry of cells into the cell cycle and subsequently regulate their passage through the cycle.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002453:Cell Cycle; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA / Q000276:immunology; D008954:Models, Biological; D011458:Prostaglandins E / Q000494:pharmacology*; D013872:Thionucleosides / Q000494:pharmacology*
D000888:Antibodies, Anti-Idiotypic; D008070:Lipopolysaccharides; D011458:Prostaglandins E; D013872:Thionucleosides; D006151:Guanosine; C037031:8-thioguanosine; D007213:Indomethacin