Prostaglandin E2 and Stem Cell Factor Can Deliver Opposing Signals to B Lymphocyte Precursors

Abstract

The synthetic prostanoid, 16,16-dimethyl PGE2, suppressed B lymphopoiesis in mice and proliferation of normal B cell precursors or the F10 pro-B cell line to interleukin 7 in culture. This was not the case with two other prostanoids, PGD2 and PGF2α, or agonists for PGI2 agonist and thromboxane A2 agonist receptors. PGE2, but not the related prostanoids or agonists, induced apoptosis in F10 cells. The apoptotic response was mediated by the EP2 class of PGE2 receptors and required an increase in intracellular cyclic adenosine 3′,5′-monophosphate, activation of protein kinase A, and protein synthesis. The influence of PGE2 on F10 cells was diminished in the presence of a cloned stromal cell line or stem cell factor. These findings describe another potential regulatory circuit in bone marrow which might influence B lymphopoiesis under disease or steady-state conditions.