title: Epstein-Barr virus infection in vitro can rescue germinal center B cells with inactivated immunoglobulin genes.
abstract: Immunoglobulin genotyping of Epstein-Barr virus (EBV)-positive posttransplantation lymphoproliferative disease has suggested that such lesions often arise from atypical post-germinal center B cells, in some cases carrying functionally inactivated immunoglobulin genes. To investigate whether EBV can rescue cells that are failed products of the somatic hypermutation process occurring in germinal centers (GCs), we isolated GC cells from tonsillar cell suspensions and exposed them to EBV in vitro. Screening more than 100 EBV-transformed cell lines of GC origin identified 6 lines lacking surface immunoglobulin, a phenotype never seen among lines derived from circulating naive or memory B cells. Furthermore, 3 of the 6 surface immunoglobulin-negative GC lines carried inactivating mutations in the immunoglobulin H (IgH) variable gene sequence. The ability of EBV to rescue aberrant products of the germinal center reaction in vitro strengthens the probability that a parallel activity contributes to EBV's lymphomagenic potential in vivo.
authors.affiliation: Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Chaganti
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Bell
authors.forename: Noelia Begue
authors.initials: NB
authors.lastname: Pastor
authors.forename: Anne E
authors.initials: AE
authors.lastname: Milner
authors.forename: Mark
authors.initials: M
authors.lastname: Drayson
authors.forename: John
authors.initials: J
authors.lastname: Gordon
authors.forename: Alan B
authors.initials: AB
authors.lastname: Rickinson
mesh_terms: D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005803:Genes, Immunoglobulin / Q000235:genetics* / Q000502:physiology*; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics