Characterization and regulation of prostaglandin E2 receptors on normal and malignant murine B lymphocytes

Prostaglandin E2 (PGE2) is a pleiotropic lipid molecule synthesized by macrophages, follicular dendritic cells, and fibroblasts, inhabitants of the B cell microenvironment. It is a potent regulator of B lymphocyte functions including activation and immunoglobulin class switching. To understand the effects of PGE2 on B lymphocyte function, the features of the putative PGE2 receptor on cells of the B lineage must be delineated. This receptor has not yet been characterized on B lymphocytes. Murine B cell lymphomas were used as a model to evaluate B lineage PGE2 receptors since they elevate intracellular cAMP in response to PGE2. Scatchard analysis indicates that the PGE2 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 compared to CH31. Interestingly, the PGE2 receptor is subject to regulation as a 20-hr LPS treatment increased PGE2 receptor number by two- to threefold on CH12 and CH31 B cell lymphomas, while dissociation constants remained similar. Finally, Scatchard analysis of normal murine splenic B lymphocytes demonstrates that they also possess high-affinity receptors for PGE2. Treatment of normal B cells with IL-4 increased PGE2 receptor levels fourfold from approximately 50 to 200 sites/cell while the affinity of the receptor slightly decreased. These results are the first to describe the number and affinity of PGE2 receptors on cells of the B lineage. These findings also suggest that B lymphocyte-activating molecules such as LPS and IL-4 may enhance sensitivity to PGE2 by upregulating the number of PGE2 receptors on B cells. Moreover, these observations may be of importance in developing strategies to specifically control the spread of PGE2-sensitive B lymphomas.