title: Beraprost enhances the APC function of B cells by upregulating CD86 expression levels.
abstract: Lipid mediators are emerging as important regulators of the immune system. Based on our previous result that shows strong expression of prostacyclin synthase in the germinal center, we investigated whether prostacyclin would regulate the APC function of B cells. Owing to the very short half-life of prostacyclin in experimental conditions, we used a more stable analog, beraprost. Beraprost increased the amounts of the costimulatory molecule CD86 but not CD80 on the surface of activated B cells in time- and dose-dependent manners. However, the enhancing effect of beraprost was not observed on memory B cells, centroblasts, and centrocytes. Beraprost required BCR and CD40 signals to upregulate CD86 expression levels. Other prostanoids such as PGE(2), 6-keto-PGF(1α), and PGF(2α) failed to alter CD86 expression levels, whereas other prostacyclin analogs were as potent as beraprost. Results carried out with receptor antagonists revealed that beraprost enhanced CD86 levels by binding to prostacyclin receptor IP and by increasing intracellular cAMP concentrations. Beraprost-treated B cells potently stimulated allogeneic T cells, which was significantly abolished by CD86 neutralization. Our data imply an unrecognized cellular and molecular mechanism about the germinal center reactions.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Korea.
authors.forename: Jini
authors.initials: J
authors.lastname: Kim
authors.forename: Chan-Sik
authors.initials: CS
authors.lastname: Park
authors.forename: Chan-Hum
authors.initials: CH
authors.lastname: Park
authors.forename: Doo-Il
authors.initials: DI
authors.lastname: Jeoung
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Jongseon
authors.initials: J
authors.lastname: Choe
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D051940:B7-2 Antigen / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000378:metabolism; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D044006:Receptors, Epoprostenol / Q000378:metabolism / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D051940:B7-2 Antigen; C497964:CD86 protein, human; D044006:Receptors, Epoprostenol; C048081:beraprost; D011464:Epoprostenol