The Journal of Immunology, Vol 147, Issue 8 2500-2506, Copyright © 1991 by American Association of Immunologists

ARTICLES

Antigen-specific IGG2A production in response to prostaglandin E2, immune complexes, and IFN-gamma

SH Stein and RP Phipps
Immunobiology Division of the Cancer Center, University of Rochester, School of Medicine and Dentistry, NY 14642.

Immune complexes (IC) can inhibit the differentiation of B lymphocytes into IgM secreting plasma cells in both Ag-specific and polyclonal systems. This report describes the ability of IC and IFN-gamma, or IFN- gamma and PGE2 to regulate the class of Ig produced in an Ag-specific system. In an in vitro model system using fluorescein (FL)-Brucella abortus as Ag, we previously showed that IC composed of an anti-FL antibody and FL-Ag inhibited the ability of FL-specific B cells to develop into IgM plaque-forming cells. In addition, PGE2 sensitized resting B cells to IC, whereas pretreatment with IL-4 alleviated the IC- mediated decrease in the IgM anti-FL response. In this manuscript, we demonstrate that IFN-gamma has antagonistic effects compared to IL-4, and potentiates the IC-induced decrease in the IgM antibody response. Interestingly, we discovered that the virtual ablation of the anti-FL IgM response exhibited by B cells treated with IC and IFN-gamma was accompanied by a dramatic increase in the anti-FL IgG2a response. Furthermore, resting B lymphocytes pulsed with IFN-gamma and PGE2, but not PGF2 alpha, exhibited augmented IgG2a production. This effect was also observed when IFN-gamma-pulsed B cells were stimulated with other agents, such as dibutyryl cAMP and cholera toxin, that elevate intracellular levels of cAMP. In addition, RpcAMP, the R-isomer of a sulfur-modified cAMP and a cAMP antagonist, inhibited anti-FL IgG2a responses. The ability of cAMP elevators such as PGE2 to promote IgG2a production, as well as to increase the frequency of IgG2a secreting cells, was demonstrated in B lymphocytes treated with IFN-gamma and polyclonally activated by LPS. Overall, our results demonstrate that IFN-gamma and PGE2-treated B lymphocytes challenged with antigen or LPS generate elevated levels of IgG2a via a cAMP-dependent pathway. These observations suggest that in vivo, PGE2 secreted by cells such as macrophages potentiates the ability of IFN-gamma to promote an IgG2a response, the predominant murine antiviral Ig.

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