CHARACTERIZATION AND REGULATION OF PROSTAGLANDIN E(2) RECEPTORS ON NORMAL AND MALIGNANT MURINE B-LYMPHOCYTES

Prostaglandin E(2) (PGE(2)) is a pleiotropic lipid molecule synthesize d by macrophages, follicular dendritic cells, and fibroblasts, inhabit ants of the B cell microenvironment. It is a potent regulator of B lym phocyte functions including activation and immunoglobulin class switch ing. To understand the effects of PGE(2) on B lymphocyte function, the features of the putative PGE(2) receptor on cells of the B lineage mu st be delineated, This receptor has not yet been characterized on B ly mphocytes, Murine B cell lymphomas were used as a model to evaluate B lineage PGE(2) receptors since they elevate intracellular cAMP in resp onse to PGE(2). Scatchard analysis indicates that the PGE(2) receptor on both CH31 and CH12 exists in a single high-affinity state, with the CH12 B lymphoma possessing three times more receptors per cell compar ed to CH31. Interestingly, the PGE(2) receptor is subject to regulatio n as a 20-hr LPS treatment increased PGE(2) receptor number by two- to threefold on CH12 and CH31 B cell lymphomas, while dissociation const ants remained similar. Finally, Scatchard analysis of normal murine sp lenic B lymphocytes demonstrates that they also possess high-affinity receptors for PGE(2). Treatment of normal B cells with IL-4 increased PGE(2) receptor levels fourfold from approximately 50 to 200 sites/cel l while the affinity of the receptor slightly decreased. These results are the first to describe the number and affinity of PGE(2) receptors on cells of the B lineage. These findings also suggest that B lymphoc yte-activating molecules such as LPS and IL-4 may enhance sensitivity to PGE(2) by upregulating the number of PGE(2) receptors on B cells, M oreover, these observations may be of importance in developing strateg ies to specifically control the spread of PGE(2)-sensitive B lymphomas . (C) 1995 Academic Press, Inc.