title: Transformation of BCR-deficient germinal-center B cells by EBV supports a major role of the virus in the pathogenesis of Hodgkin and posttransplantation lymphomas.
abstract: In classic Hodgkin lymphoma (HL) and posttransplantation lymphoproliferative disease (PTLD), 2 malignancies frequently associated with Epstein-Barr virus (EBV), the tumor cells often appear to derive from B-cell receptor (BCR)-deficient and therefore preapoptotic germinal center (GC) B cells. To test whether EBV can rescue BCR-less GC B cells, we infected human tonsillar CD77+ GC B cells in vitro with EBV. More than 60 monoclonal lymphoblastoid cell lines (LCLs) were established. Among these, 28 cell lines did not express surface immunoglobulin (sIg). Two of the sIg-negative cell lines carry obviously destructive mutations that have been introduced into originally functional V(H) gene rearrangements during the process of somatic hypermutation. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) showed that in most other lines the sIg deficiency was not simply the result of transcriptional down-regulation, but it was rather due to posttranscriptional defects. These findings strongly support the idea that EBV plays a central role in the pathogenesis of classic HL and PTLD by rescuing BCR-deficient, preapoptotic GC B cells from apoptosis, and that EBV infection renders the cells independent from survival signals normally supplied by a BCR. The monoclonal LCLs represent valuable models for early stages of lymphoma development in classic HL and PTLD.
authors.affiliation: Institute for Cell Biology (Tumor Research), University of Duisburg-Essen, Virchowstr. 173, 45122 Essen, Germany. doerte.bechtel@uni-duisburg-essen.de
authors.forename: Dörte
authors.initials: D
authors.lastname: Bechtel
authors.forename: Julia
authors.initials: J
authors.lastname: Kurth
authors.forename: Claus
authors.initials: C
authors.lastname: Unkel
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
mesh_terms: D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D018858:Germinal Center / Q000276:immunology / Q000473:pathology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006689:Hodgkin Disease / Q000235:genetics / Q000473:pathology* / Q000821:virology; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D008223:Lymphoma / Q000209:etiology / Q000235:genetics / Q000473:pathology* / Q000821:virology; D008969:Molecular Sequence Data; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000172:deficiency* / Q000235:genetics; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell