Prostaglandin E2 and cAMP promote B lymphocyte class switching to IgG1.
Prostaglandins of the E series (PGE) have traditionally been considered as suppressive for immune responses; however, recent data suggest that PGE channels the immune response towards a T helper 2 type response and production of selected immunoglobulin isotypes. Herein, we present data showing that PGE(2) and other agents that induce intracellular rises in cAMP significantly increased B lymphocyte IgG1 production (up to sevenfold). PGE(2) acted on small resting B cells and on uncommitted B cells expressing high levels of surface IgM to increase the number of cells secreting IgG1. PGE(2) even increased IgG1 synthesis by purified B cells in the absence of exogenous IL-4. Finally, PGE(2) synergized with IL-4 to induce germline gamma1 transcripts through the switch region. This transcription is required for isotype switching. These data support the hypothesis that PGE(2) acts on uncommitted resting B cells at the level of germline gamma1 transcription to promote class switching to IgG1. PGE(2) is an important regulator of the immune response, shifting the balance towards a T helper type 2 response, directing selection of the isotypes produced, and promoting memory cell formation.
Roper
Rachel L
RL
Department of Environmental Medicine, James P. Wilmot Cancer Center, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.
Graf
Beth
B
Phipps
Richard P
RP
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000276:immunology / Q000494:pharmacology; D015232:Dinoprostone / Q000276:immunology / Q000494:pharmacology*; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D017578:Immunoglobulin Class Switching / Q000187:drug effects* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D015847:Interleukin-4; D000242:Cyclic AMP; D015232:Dinoprostone