REGULATORY EFFECTS OF PROSTAGLANDIN-E2 ON THE GROWTH AND DIFFERENTIATION OF HUMAN B-LYMPHOCYTES ACTIVATED THROUGH THEIR CD40 ANTIGEN

We have studied the effects of prostaglandin E(2) (PGE(2)) on the grow th and differentiation of human tonsillar B lymphocytes cultured in th e CD40 system with or without IL-4 or IL-10. PGE(2) (10(-9) to 10(-6) M) enhanced proliferation of B cells activated through their CD40 Ag, but not their Ig secretion. PGE(2) further potentiated both IL-4- and IL-10-induced B cell growth as determined by [H-3]TdR uptake and cellu lar enumeration. The IL-10-induced IgM, IgG, and IgA secretion was enh anced twofold to fourfold after addition of PGE(2), whereas IL-4-induc ed IgG and IgE secretion was inhibited. The IgE production was particu larly sensitive as an approximate to 90% inhibition was obtained for 1 0(-7) M PGE(2). In addition, PGE(2) inhibited IgE production by naive surface IgD(+) B cells cultured in the CD40 system, suggesting that PG E(2) may interact with mechanisms involved in IgE switching. PGE(2) di splayed similar effects on cytokine-induced proliferation and Ig secre tion of B cells activated by anti-CD40 Abs used in a soluble form. Fin ally, the PGE(2) effects were mimicked by agents increasing cAMP, indi cating that the PGE(2) activities are likely to depend on the activati on of the cAMP pathway. Altogether, the present data indicate that PGE (2) stimulates human CD40-activated B cell growth, but differently mod ulates cytokine-induced differentiation. Thus, in microenvironments su pporting the development of an immune response, the secretion of PGE(2 ) by competent cells such as macrophages may participate in the regula tion of the humoral response.