Prostaglandin E2 inhibits B lymphocyte activation by a cAMP-dependent mechanism: PGE-inducible regulatory proteins.
We have previously shown that macrophage-secreted prostaglandins of the E series (PGE) and other agents which increase cAMP inhibit IgM production and proliferation of murine B lymphocytes. In this study, we show that PGE2 inhibits B cell activation events including enlargement, class II MHC hyperexpression, and the expression of the low-affinity receptor for IgE, Fc epsilon RII/CD23 (35-50%) in a cAMP-dependent manner. PGE action is mimicked by other cAMP-inducing agents and is inhibited by RpcAMP (a nonhydrolyzable cAMP analog which is a competitive inhibitor of cAMP-dependent protein kinase A). PGE2 could inhibit enlargement and upregulation of activation Ag even if preincubated with cells and then washed out prior to B cell stimulation. This change in B cell phenotype was abrogated if the reversible protein synthesis inhibitor cycloheximide was included during B cell incubation with PGE2. To identify the newly synthesized cAMP- and PGE-inducible regulatory proteins (PIRP), two-dimensional gel electrophoresis of lysates of B lymphocytes treated +/- PGE2 was performed. This report is the first to identify putative PIRP proteins. The roles of PIRP in PGE regulation of B cell activation and class switching are discussed.
Roper
R L
RL
Immunology and Immunotherapy Division of the Cancer Center, University of Rochester School of Medicine and Dentistry, New York 14642.
Ludlow
J W
JW
Phipps
R P
RP
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D000242:Cyclic AMP / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D014176:Protein Biosynthesis; D017455:Receptors, IgE / Q000032:analysis; D014157:Transcription Factors / Q000502:physiology*
D000949:Histocompatibility Antigens Class II; D017455:Receptors, IgE; D014157:Transcription Factors; D003513:Cycloheximide; D000242:Cyclic AMP; D015232:Dinoprostone