title: Innate apoptosis of human B lymphoblasts transformed by Epstein-Barr virus: modulation by cellular immortalization and senescence.
abstract: B-lymphoblastoid cell lines (LCLs) transformed by Epstein-Barr virus have a phenotype corresponding to activated B-lymphoblasts. Although they are widely used as models in various biological and medical studies, their innate morphological differentiation and apoptosis has been little studied. We report here that a large proportion of LCL cells spontaneously differentiate into smaller lymphoid cells which ultimately undergo apoptosis during conventional cell culture. Two distinct types of apoptosis with some intermediate types exist: type 1 apoptosis in small and medium-size cells with shrunken nuclei having heavily condensed chromatin in the whole nucleus region accompanied by relatively large internucleosomally fragmented DNA (above 2 kbp); type 2 apoptosis in large lymphoblasts with extremely lobulated nuclei having chromatin condensation beneath the nuclear membrane alone accompanied by smaller internucleosomally fragmented DNA (below 2 kbp). Type 1 apoptotic cells were far more numerous than type 2 apoptotic cells. The incidence of type 1 apoptosis was suppressed by cellular immortalization and was extremely stimulated at the end of the lifespan (crisis). These results provide essential information for us to use LCLs for various biological and medical studies including cellular immortalization, tumorigenesis and senescence.
authors.affiliation: GeneCare (previously AGENE) Research Institute, 200 Kajiwara, Kamakura, Kanagawa 247-0063, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Satoh
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Yasuda
authors.forename: Toru
authors.initials: T
authors.lastname: Higaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Goto
authors.forename: Sei-ichi
authors.initials: S
authors.lastname: Tanuma
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ide
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Furuichi
authors.forename: Masanobu
authors.initials: M
authors.lastname: Sugimoto
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001402:B-Lymphocytes / Q000473:pathology / Q000648:ultrastructure / Q000821:virology*; D002454:Cell Differentiation / Q000235:genetics*; D002461:Cell Line, Transformed / Q000648:ultrastructure / Q000821:virology*; D002467:Cell Nucleus / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D016922:Cellular Senescence / Q000235:genetics; D002843:Chromatin / Q000473:pathology / Q000648:ultrastructure; D053938:DNA Fragmentation / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics*; D008854:Microscopy, Electron; D013234:Stem Cells / Q000648:ultrastructure / Q000821:virology*
chemical_list: D002843:Chromatin