DIFFERENTIAL REGULATION OF SURFACE-IMMUNOGLOBULIN AND LYB2 MEDIATED B-CELL ACTIVATION .2. CAMP-DEPENDENT (PROSTAGLANDIN-E(2)) AND INDEPENDENT (IFN-GAMMA) MECHANISMS OF REGULATION OF B-LYMPHOCYTE ACTIVATION

We have recently demonstrated that pharmacological agents that elevate d cAMP inhibited sIgM but not Lyb2 mediated activation of murine B lym phocytes. In this report we show evidence for differential regulation of prostaglandin E2 (PGE2), a physiological agent that elevated cAMP a nd IFN-gamma on sIgM and Lyb2 mediated B cell activation. PGE2 inhibit ed anti-IgM but not anti-Lyb2 induced DNA synthesis in a dose-dependen t manner. Interestingly, rIFN-gamma also inhibited anti-Ig but not ant i-Lyb2 induced DNA synthesis. rIFN-gamma exerted its effects directly on B cells since depletion of T cells and G-10 Sephadex adherent cells did not alter effects of IFN-gamma on anti-IgM and anti-Lyb2 induced DNA synthesis. Pretreatment of B cells with IL-4 and/or IL-5 did not p revent the IFN-gamma mediated inhibition of the anti-IgM response. The inhibitory effect of IFN-gamma was observed during early stages of B cell activation. Thus IFN-gamma inhibited anti-mu induced blast transf ormation and subsequent progression into the G1 phase of the cell cycl e. The differential effects exerted by PGE2 and rIFN-gamma appeared to be mediated by distinct mechanisms. Thus PGE2 but not rIFN-gamma, at concentrations inhibitory to the sIgM response, induced elevation of i ntracellular cAMP levels. These results demonstrate that physiological ly relevant immunomodulators such as PGE2 and IFN-gamma can differenti ally regulate murine B cell responses mediated through the antigen rec eptor and Lyb2 molecules by cAMP dependent and independent mechanisms. Relevance of this regulation for the induction of antibody synthesis by T(h)1 and T(h)2 types of helper T cells is discussed.