title: B-cell lymphoproliferation and lymphomagenesis are associated with clonotypic intracellular terminal regions of the Epstein-Barr virus.
abstract: We analyzed 17 B-cell lineages cloned from two patients with infectious mononucleosis and found that different B-cell lineages exhibited notable variation in the length of the fused Epstein-Barr virus (EBV) terminal region on intracellular EBV episomes. EBV termini in different B-cell clones from the same person differed by as many as 15 to 20 reiterations of the ca. 500-base-pair terminal repeat sequence. In contrast, analysis of seven B-cell lineages cloned from a patient with a fatal, oligoclonal lymphoma revealed that three of the cell clones had the same-sized EBV terminal region. These three clones had previously been shown, by immunoglobulin gene analysis, to be metastatic daughter cells descended from a common progenitor. Similarity of the EBV terminal regions in the three daughter clones suggested that EBV infected the progenitor cell before proliferation and metastasis. Individual, EBV-infected cells from a single individual showed sufficient heterogeneity in their EBV termini to allow use of terminal fragment size as a clonal marker in studies addressing the contribution of EBV to the clonal pathogenesis of tumors with which this virus has been associated.
authors.affiliation: Department of Pediatrics, University of California, Los Angeles School of Medicine 90024.
authors.forename: N A
authors.initials: NA
authors.lastname: Brown
authors.forename: C R
authors.initials: CR
authors.lastname: Liu
authors.forename: Y F
authors.initials: YF
authors.lastname: Wang
authors.forename: C R
authors.initials: CR
authors.lastname: Garcia
mesh_terms: D001402:B-Lymphocytes / Q000382:microbiology*; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000382:microbiology / Q000473:pathology*; D002455:Cell Division; D002999:Clone Cells / Q000473:pathology; D004262:DNA Restriction Enzymes; D004273:DNA, Neoplasm / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D007244:Infectious Mononucleosis / Q000382:microbiology / Q000473:pathology*
chemical_list: D004273:DNA, Neoplasm; D004279:DNA, Viral; D004262:DNA Restriction Enzymes