Splawski J B, Lipsky P E
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
J Immunol. 1994 Jun 1;152(11):5259-67.
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.
前列腺素E2（PGE2）可抑制金黄色葡萄球菌和白细胞介素-2刺激的成年B细胞产生免疫球蛋白（Ig），并抑制抗CD3刺激的T细胞产生白细胞介素-2。相比之下，PGE2并不抑制成年B细胞依赖T细胞的Ig产生。然而，即使在补充白细胞介素-2的情况下，PGE2也能显著抑制新生B细胞依赖T细胞的Ig分泌。福斯高林（一种腺苷酸环化酶的直接激活剂）和二丁酰环磷腺苷（dbcAMP）也产生类似的效果。PGE2抑制新生CD5+和CD5- B细胞依赖T细胞的Ig分泌，但不抑制CD5+或CD5-成年外周血B细胞的Ig分泌。PGE2不抑制白细胞介素-2依赖的抗CD3刺激的新生T细胞增殖或T细胞依赖的新生B细胞增殖。当延迟添加PGE2时，其可抑制新生B细胞的Ig产生，这表明初始B细胞的激活和增殖未被阻断，但PGE2阻止了随后的分化。此外，PGE2抑制新生T细胞的辅助作用，且与细胞因子的产生无关。PGE2诱导的新生B细胞和T细胞中的环磷腺苷（cAMP）水平与成年细胞中的水平并无差异。这些结果表明，新生淋巴细胞产生Ig对诸如PGE2等能提高cAMP水平的药物的抑制作用具有独特的敏感性。这种敏感性可能导致人类新生B细胞在体内的反应受到抑制。
