title: Inhibition of cell growth and Epstein-Barr virus reactivation by CD40 stimulation in Epstein-Barr virus-transformed B cells.
abstract: The CD40 molecule plays important roles in B cell activation, proliferation, and immunoglobulin (Ig) class switching. In Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL), CD40 mediates growth inhibition and EBV reactivation via the CD40 signaling pathways. CD40 cross-linking with a monoclonal antibody arrests cell growth in G1 and induces expression of p27kip1 cyclin-dependent kinase inhibitor. CD40 cross-linking also induces EBV reactivation, as detected by the induction of EBV-specific early antigen, immediate early BZLF1 RNA, and its protein product ZEBRA. These results support hypotheses that the proliferation of EBV-infected B cells in vivo can be inhibited by interactions with the CD40 ligand on activated helper T cells, and latent EBV is reactivated via the signaling pathways controlled by CD40 interactions.
authors.affiliation: Department of Biosignaling School of Life Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: T A
authors.initials: TA
authors.lastname: Satoh
authors.forename: M
authors.initials: M
authors.lastname: Takanashi
authors.forename: K
authors.initials: K
authors.lastname: Hirai
authors.forename: E
authors.initials: E
authors.lastname: Ohnishi
authors.forename: T
authors.initials: T
authors.lastname: Sairenji
mesh_terms: D017209:Apoptosis; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology* / Q000821:virology; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D008213:Lymphocyte Activation; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins; D014775:Virus Activation; D017735:Virus Latency
chemical_list: D019013:CD40 Antigens; D018797:Cell Cycle Proteins; D007075:Immunoglobulin M; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D023201:CD40 Ligand; D050760:Cyclin-Dependent Kinase Inhibitor p27