Inhibition of human B cell responsiveness by prostaglandin E₂

The capacity of prostaglandin E₂ (PGE₂) to modulate human peripheral blood B cell proliferation and the generation of immunoglobulin-secreting cells (ISC) stimulated by Cowan 1 strain Staphylococcus aureus and mitogen-stimulated T cell supernatant was examined. PGE₂ significantly inhibited both responses, whereas PGF(2α) had no inhibitory effect. Responses of highly purified B cells obtained from spleen, lymph node, and tonsil were also inhibited. In addition PGE₂ suppressed B cell responses supported by recombinant interleukin 2 rather than T cell supernatant. PGE₂-mediated inhibition was mimicked by forskolin, a direct activator of adenylate cyclase. Kinetic studies indicated that PGE₂ inhibited B cell responses by a progressively greater increment as cultures were prolonged. Evaluation by flow cytometry after staining with acridine orange or mithramycin indicated that PGE₂ had no effect on initial B cell entry into the G₁ phase of the cell cycle, passage through G₁, and entry into S, G₂, and M. Rather, PGE₂ inhibited responses of postdivisional daughter cells. PGE₂ inhibited responses in cultures stimulated by the calcium ionophore ionomycin and T cell supernatant but had minimal effects in cultures stimulated by the combination of ionomycin and phorbol myristate acetate. Moreover, phorbol myristate acetate reversed PGE₂-mediated inhibition of proliferation stimulated by S. aureus or S. aureus + T cell supernatant. These results indicate that PGE₂ suppresses the continued growth and differentiation of human B cells, although it has no effect on initial B cell activation and suggest that PGE₂ may play a role in regulating human B cell responses in vivo.