Human follicular dendritic cells express prostacyclin synthase: a novel mechanism to control T cell numbers in the germinal center.
Stromal cells in the lymphoid organs provide a microenvironment where lymphocytes undergo various biological processes such as development, homing, clonal expansion, and differentiation. Follicular dendritic cells (FDCs) in the primary and secondary follicles of the peripheral lymphoid tissues interact with lymphocytes by contacting directly or producing diffusible molecules. To understand the biological role of human FDC at the molecular level, we developed a mAb, 3C8, that recognizes FDC but not bone marrow-derived cells. Through expression cloning and proteome analysis, we identified the protein that is recognized by 3C8 mAb, which revealed that FDC expresses prostacyclin synthase. The 3C8 protein purified from FDC-like cells indeed displayed the enzymatic activity of prostacyclin synthase and converted PGH2 into prostacyclin. In addition, prostacyclin significantly inhibited proliferation of T cells but delayed their spontaneous apoptosis. These findings may help explain why T cells constitute only a minor population compared with B cells in the germinal center.
Lee
In Yong
IY
Department of Microbiology and Immunology, Kangwon National University College of Medicine, Chunchon, Kangwon, Republic of Korea.
Ko
Eun-Mi
EM
Kim
Sang-Hyun
SH
Jeoung
Doo-Il
DI
Choe
Jongseon
J
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000302:isolation & purification; D020566:Dendritic Cells, Follicular / Q000201:enzymology* / Q000276:immunology*; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D018858:Germinal Center / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000096:biosynthesis* / Q000302:isolation & purification; D018655:Lymphocyte Count; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000201:enzymology / Q000276:immunology
D006131:Growth Inhibitors; C048081:beraprost; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase