Induction of interleukin-6 after stimulation of human B-cell CD21 by Epstein-Barr virus glycoproteins gp350 and gp220.
The cellular receptor for Epstein-Barr virus (EBV) is the type 2 complement receptor, CD21. At initial infection, EBV virion glycoproteins gp350 and gp220 bind to CD21. We report here that the cross-linking of CD21 by gp350/220 results in increased amounts of interleukin 6 (IL-6) RNA and IL-6 protein. This effect could be blocked with anti-gp350/220 and anti-CD21 monoclonal antibodies. Induction of IL-6 in B cells by EBV could be mimicked by treatment with the protein kinase C (PKC) activator phorbol 12,13-dibutyrate but not with the calcium ionophore ionomycin. IL-6 induction by EBV was inhibited with the PKC-specific inhibitor bisindolylmaleimide or the protein tyrosine kinase inhibitors methyl 2,5-dihydroxycinnamate and herbimycin A, indicating that the induction of IL-6 following CD21 cross-linking is mediated through PKC- and protein tyrosine kinase-dependent pathways.
Laboratory of Virology, Children's Hospital of Eastern Ontario, Canada.
J E
JE
Tanner
C
C
Alfieri
T A
TA
Chatila
F
F
Diaz-Mitoma
D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000276:immunology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D014763:Viral Matrix Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015850:Interleukin-6; D012333:RNA, Messenger; D017464:Receptors, Complement 3d; D014763:Viral Matrix Proteins; D015240:Phorbol 12,13-Dibutyrate