Regulation of B cell tolerance by macrophage-derived mediators: antagonistic effects of prostaglandin E2 and interleukin 1.
A role for prostaglandins in the mechanism of B cell tolerance induction in normal adult mouse spleen cells was examined. Two inhibitors of the cyclooxygenase pathway of arachidonic acid metabolism, indomethacin and acetylsalicylic acid, abrogated hapten-specific B cell tolerance induction by trinitrophenyl-human gamma-globulin. Tolerance was fully restored by the addition of prostaglandin E2 (PGE2) at a concentration of greater than or equal to 6 nM. T cell-depleted spleen cells produced comparable amounts of PGE2 in culture, indicating that the tolerance promoting activity of PGE2 occurred with physiologically relevant concentrations. Depletion and reconstitution experiments indicated that macrophages in the spleen cell preparations completely accounted for both PGE2 production and the effects of indomethacin and acetylsalicylic acid on B cell tolerance induction. The macrophage product interleukin 1 (IL 1) was also found to alter B cell susceptibility to tolerance induction. Thus, human IL 1 containing monocyte supernatants and purified IL 1 were found to interfere with B cell tolerance induction when added to macrophage- and T cell-depleted splenic B cells. Tolerance was restored in such cultures by the addition of 10 nM PGE2. These experiments demonstrate that within mixed lymphoid populations macrophages through the release of mediators modulate B cell susceptibility to tolerance induction.
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Goldings
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D000939:Epitopes / Q000276:immunology; D005260:Female; D006241:Haptens / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D015846:Monokines; D011458:Prostaglandins E / Q000494:pharmacology*; D011506:Proteins / Q000502:physiology
D016861:Cyclooxygenase Inhibitors; D000939:Epitopes; D006241:Haptens; D007375:Interleukin-1; D015846:Monokines; D011458:Prostaglandins E; D011506:Proteins; D015232:Dinoprostone; D007213:Indomethacin