The Journal of Immunology, Vol 138, Issue 4 1074-1081, Copyright © 1987 by American Association of Immunologists

ARTICLES

Inhibition of human B cell responsiveness by prostaglandin E2

NJ Simkin, DF Jelinek and PE Lipsky

The capacity of prostaglandin E2 (PCE2) 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 PGF2 alpha 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.

This article has been cited by other articles:

				P. K. A. Mongini, J. K. Inman, H. Han, R. J. Fattah, S. B. Abramson, and M. Attur APRIL and BAFF Promote Increased Viability of Replicating Human B2 Cells via Mechanism Involving Cyclooxygenase 2. J. Immunol., June 1, 2006; 176(11): 6736 - 6751. [Abstract] [Full Text] [PDF]

				S. Naderi, K. B. Gutzkow, H. U. Lahne, S. Lefdal, W. J. Ryves, A. J. Harwood, and H. K. Blomhoff cAMP-induced degradation of cyclin D3 through association with GSK-3{beta} J. Cell Sci., August 1, 2004; 117(17): 3769 - 3783. [Abstract] [Full Text] [PDF]

				R. Ikegami, Y. Sugimoto, E. Segi, M. Katsuyama, H. Karahashi, F. Amano, T. Maruyama, H. Yamane, S. Tsuchiya, and A. Ichikawa The Expression of Prostaglandin E Receptors EP2 and EP4 and Their Different Regulation by Lipopolysaccharide in C3H/HeN Peritoneal Macrophages J. Immunol., April 1, 2001; 166(7): 4689 - 4696. [Abstract] [Full Text] [PDF]

				M. Savard, C. Belanger, M. J. Tremblay, N. Dumais, L. Flamand, P. Borgeat, and J. Gosselin EBV Suppresses Prostaglandin E2 Biosynthesis in Human Monocytes J. Immunol., June 15, 2000; 164(12): 6467 - 6473. [Abstract] [Full Text] [PDF]