Macrophage-secreted prostaglandin E2 potentiates immune complex-induced B cell unresponsiveness.
Immune complexes (IC) are potent modulators of immune responses. In this report, we used an in vitro murine model system to investigate how two types of accessory cells pulsed with IC regulated B cell function. We demonstrate that IC-pulsed macrophages (M phi) induce hapten-specific B cell unresponsiveness, whereas IC-pulsed splenic lymphoid dendritic cells (LDC) and and LDC-like tumor line caused an augmentation of the antibody response. The mechanism by which IC-pulsed M phi diminished antibody production required two signals. The first was an antigen-specific signal supplied by the IC, and the second a nonspecific co-factor which was a product of M phi cyclo-oxygenase metabolism. Specifically, it was shown that prostaglandin E2 (PGE2) could function at this co-factor. Interestingly, other prostanoids, such as PGF2 alpha, did not function in this fashion. Purified fluorescein (FL+)-specific B cells pulsed with IC exhibited a similar pattern of hapten-specific unresponsiveness. Treatment of accessory cell-free, FL+B cells with PGE2 rendered them sensitive to subtolerogenic doses of soluble IC. Overall, our results suggest that one mechanism by which unresponsiveness can be induced involves both IC and PGE2, and that elevated levels of PGE2 sensitize B lymphocytes to antigen-specific tolerogenic signals.
Stein
S H
SH
Immunology Unit, University of Rochester School of Medicine and Dentistry, New York 14642.
Phipps
R P
RP
D000818:Animals; D000917:Antibody Formation; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D006241:Haptens; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008264:Macrophages / Q000502:physiology*; D051379:Mice
D000936:Antigen-Antibody Complex; D006241:Haptens; D015232:Dinoprostone; D007213:Indomethacin