SELECTIVE REGULATION OF ANTIGEN-SPECIFIC IGE RESPONSE BY CYCLIC-AMP LEVEL IN MURINE LYMPHOCYTES

We have reported that prostaglandin E2 (PGE2) is a selective stimulator of the antigen-specific IgE response [6]. Because PGE2 is known to elevate intracellular cAMP, we investigated the regulatory role of cAMP in the production of antigen-specific IgE. Anti-TNP IgE response was induced by stimulating TNP-KLH-primed BALB/c spleen cells with the same antigen in vitro. Addition of 10-100 muM dibutyryl cAMP (DBcAMP) to the lymphocyte culture resulted in a 2-3-fold increase in anti-TNP IgE response without affecting the production of anti-TNP IgG1 or IgM. Forskolin, a stimulator of adenylate cyclase, also specifically augmented the IgE response. In contrast, 2',5'-dideoxyadenosine, an inhibitor of adenylate cyclase, suppressed IgE production in an isotype-specific manner. These results suggest that IgE synthesis can be selectively modulated by intracellular cAMP level. Enhancement of IgE production by DBcAMP was observed, particularly in highly primed spleen cells, suggesting that IgE-committed B cells are subjected to regulation by cAMP.