Prostaglandin E2 inhibits T cell-dependent Ig secretion by neonatal but not adult lymphocytes.
Prostaglandin E2 (PGE2) inhibits Ig production by adult B cells stimulated with Staphylococcus aureus and IL-2, and inhibits the production of IL-2 by anti-CD3 stimulated T cells. By contrast, PGE2 did not inhibit T cell-dependent Ig production by adult B cells. However, T cell-dependent Ig secretion by neonatal B cells was markedly inhibited by PGE2 even in the presence of supplemental IL-2. Forskolin, a direct activator of adenylate cyclase, and dibutyryl cAMP caused similar effects. PGE2 inhibited T cell-dependent Ig secretion by both neonatal CD5+ and CD5- B cells but did not inhibit Ig secretion by either CD5+ or CD5- adult peripheral blood B cells. PGE2 did not inhibit IL-2-dependent anti-CD3 stimulated neonatal T cell proliferation or T cell-dependent neonatal B cell proliferation. PGE2 inhibited neonatal B cell Ig production when addition was delayed, suggesting that initial B cell activation and proliferation were not blocked, but that PGE2 prevented subsequent differentiation. In addition, PGE2 inhibited neonatal T cell help independent of cytokine production. PGE2-induced cAMP levels in neonatal B and T cells were not different from adult levels. These results indicate that production of Ig by neonatal lymphocytes is uniquely sensitive to the inhibitory effects of agents such as PGE2 that elevate cAMP levels. This sensitivity may contribute to the suppressed in vivo responses of human neonatal B cells.
Splawski
J B
JB
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
Lipsky
P E
PE
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D018956:CD5 Antigens; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D016207:Cytokines / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D007231:Infant, Newborn; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000502:physiology*
D015703:Antigens, CD; D018956:CD5 Antigens; D016207:Cytokines; D007136:Immunoglobulins; D000242:Cyclic AMP; D015232:Dinoprostone