PROSTAGLANDIN E(2) INHIBITS B-LYMPHOCYTE ACTIVATION BY A CAMP-DEPENDENT MECHANISM - PGE-INDUCIBLE REGULATORY PROTEINS

We have previously shown that macrophage-secreted prostaglandins of th e E series (PGE) and other agents which increase cAMP inhibit IgM prod uction and proliferation of murine B lymphocytes. In this study, we sh ow that PGE(2) inhibits B cell activation events including enlargement , class II MHC hyperexpression, and the expression of the low-affinity receptor for IgE, Fc epsilon RII/ CD23 (35-50%) in a cAMP-dependent m anner. PGE action is mimicked by other cAMP-inducing agents and is inh ibited by RpcAMP (a nonhydrolyzable cAMP analog which is a competitive inhibitor of cAMP-dependent protein kinase A). PGE(2) could inhibit e nlargement 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 in hibitor cycloheximide was included during B cell incubation with PGE(2 ). To identify the newly synthesized cAMP- and PGE-inducible regulator y proteins (PIRP), two-dimensional gel electrophoresis of lysates of B lymphocytes treated +/- PGE(2) was performed. This report is the firs t to identify putative PIRP proteins. The roles of PIRP in PGE regulat ion of B cell activation and class switching are discussed. (C) 1994 A cademic Press, Inc.