title: Cell phenotype (CD23)-dependent variation in EBV genome copy numbers within lymphoblastoid cell lines (LCL).
abstract: Three Epstein-Barr-virus-transformed lymphoblastoid cell lines (LCL) were analysed on the basis of their CD23 expression. Levels of EBV-DNA were compared in the positive and negative subpopulations. Two lines were further analysed with regard to EBNA, cytoplasmic immunoglobulin (cIg) and lytic (EA/VCA) protein expression. Both subpopulations had a similar MHC class-II transcription, but the CD23- subpopulation had a lower plating efficiency and a lower rate of DNA synthesis. In the B6, NAD50 and 0467.3 cell lines, CD23- cells contained 2 +/- 0.2 - 6.4 +/- 3.0 times less EBV DNA than the corresponding CD23+ population. EBNA was expressed in 81 +/- 4.2% - 93 +/- 3.8% of the CD23+ cells and in 0 - 46 +/- 8.0% of the CD23- cells. No CD23+ cells in B6 or NAD50 contained any EA/VCA, while 19 +/- 2.8% - 24 +/- 4.2% of the CD23- cells were positive for the lytic-cycle-associated antigens. Of the CD23- cells, 70 +/- 8.6% - 86 +/- 6.0% were positive for cytoplasmic immunoglobulin compared to 14.7 +/- 2.7% - 14.9 +/- 1.8% in the corresponding CD23+ population. We have previously shown that only 18% of the cIg-positive cells were EBNA-positive in the B6 line compared to 94% in the cIg- population. This was open to 2 alternative interpretations: loss of EBV genomes from a fraction of the cells with subsequent differentiation to secretory immunoglobulin production, or down-regulation of EBNA expression in differentiating, EBV-genome-positive cells. Our present findings speak for the first alternative, indicating that a certain proportion of the cells may lose their EBV genomes in both long-established and freshly transformed LCLs. This is accompanied by a reduced percentage of EBNA-positive cells, the disappearance of at least one activation marker (CD23) associated with the virally induced blast transformation, and an increased synthesis of cIg.
authors.affiliation: Department of Medical Cell Genetics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: V
authors.initials: V
authors.lastname: Wendel-Hansen
authors.forename: W
authors.initials: W
authors.lastname: Tao
authors.forename: M
authors.initials: M
authors.lastname: Ericson
authors.forename: G
authors.initials: G
authors.lastname: Klein
authors.forename: A
authors.initials: A
authors.lastname: Rosén
mesh_terms: D000917:Antibody Formation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D000956:Antigens, Viral / Q000378:metabolism; D036022:Capsid Proteins; D002455:Cell Division; D002478:Cells, Cultured; D019309:Epstein-Barr Virus Nuclear Antigens; D004854:Herpesvirus 4, Human / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism; D066298:In Vitro Techniques; D016131:Lymphocyte Subsets / Q000382:microbiology*; D011961:Receptors, Fc / Q000502:physiology*; D017455:Receptors, IgE; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000956:Antigens, Viral; D036022:Capsid Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; C041788:Epstein-Barr viral capsid antigen; D011961:Receptors, Fc; D017455:Receptors, IgE; D014764:Viral Proteins