Differential regulation of surface immunoglobulin and Lyb2 mediated B cell activation: II. Camp dependent (prostaglandin E₂) and independent (IFN-_γ) mechanisms of regulation of B lymphocyte activation

We have recently demonstrated that pharmacological agents that elevated cAMP inhibited sigM but not Lyb2 mediated activation of murine B lymphocytes. In this report we show evidence for differential regulation of prostagiandin E₂ (PGE₂), a physiological agent that elevated cAMP and IFN-_γ on sigM and Lyb2 mediated B cell activation. PGE₂ inhibited anti-lgM but not anti-Lyb2 induced DNA synthesis in a dose-dependent manner. Interestingly, rlFN-_γ also inhibited anti-lgM but not anti-Lyb2 induced DNA synthesis. rlFN-_γ exerted its effects directly on B cells since depletion of T cells and G-10 Sephadex adherent cells did not alter effects of IFN-_γ on anti-lgM and anti-Lyb2 induced DNA synthesis. Pretreatment of B cells with IL-4 and/or IL-5 didnot prevent the IFN-_γ mediated inhibition of the anti-lgM response. The inhibitory effect of IFN-_γ was observed during early stages of B cell activation. Thus IFN-_γ inhibited anti-μ induced blast transformation and subsequent progression into the G₁ phase of the cell cycle. The differential effects exerted by PGE₂ and rIFN-_γ appeared to be mediated by distinct mechanisms.Thus PGE₂ but not rIFN-_γ, at concentrations inhibitory to the slgM response, induced elevation of intracellular cAMP levels. These results demonstrate that physiologically relevant immunomodulators such as PGE₂ and IFN-_γ can differentially regulate murine B cell responses mediated through the antigen receptor and Lyb2 molecules by cAMP dependent and independent mechanisms. Relevance of this regulation for the induction of antibody synthesis by T_h1 and T_h2 types of helper T cells is discussed.