Prostaglandin E2 Inhibits B Lymphocyte Activation by a cAMP-Dependent Mechanism: PGE-Inducible Regulatory Proteins

We have previously shown that macrophage-secreted prostaglandins of the E series (PGE) and other agents which increase cAMP inhibit IgM production and proliferation of murine B lymphocytes. In this study, we show that PGE2 inhibits B cell activation events including enlargement, class II MHC hyperexpression, and the expression of the low-affinity receptor for IgE, FcϵRII/CD23 (35-50%) in a cAMP-dependent manner. PGE action is mimicked by other cAMP-inducing agents and is inhibited by RpcAMP (a nonhydrolyzable cAMP analog which is a competitive inhibitor of cAMP-dependent protein kinase A). PGE2 could inhibit enlargement and upregulation of activation Ag even if preincubated with cells and then washed out prior to B cell stimulation. This change in B cell phenotype was abrogated if the reversible protein synthesis inhibitor cycloheximide was included during B cell incubation with PGE2. To identify the newly synthesized cAMP- and PGE-inducible regulatory proteins (PIRP), two-dimensional gel electrophoresis of lysates of B lymphocytes treated ± PGE2 was performed. This report is the first to identify putative PIRP proteins. The roles of PIRP in PGE regulation of B cell activation and class switching are discussed.