title: Epstein-Barr virus-infected B cells expanding in germinal centers of infectious mononucleosis patients do not participate in the germinal center reaction.
abstract: To assess the impact of the germinal center (GC) reaction on viral spread in Epstein-Barr virus (EBV) infection, we isolated EBV(+) GC B cells from the tonsils of two infectious mononucleosis patients, sequenced their rearranged V genes, and determined expression of the EBV latency genes EBV nuclear antigen 2 and latent membrane protein 1. Most EBV(+) GC B cells belonged to clones of cells harboring somatically mutated V gene rearrangements. Ongoing somatic hypermutation, the hallmark of the GC reaction, was seen only in uninfected GC B cell clones, not in EBV(+) B cell clones. Thus, in infectious mononucleosis, GC and/or memory B cells are directly infected by EBV and expand without somatic hypermutation, whereas the GC passage of EBV-infected naive B cells does not contribute detectably to the generation of infected memory B cells, the main reservoir of EBV during persistence. Most, if not all, EBV-infected cells in GCs exhibited an unusual EBV gene expression pattern in that they were positive for EBV nuclear antigen 2 but negative for latent membrane protein 1. Although the three main types of EBV-associated B cell lymphomas (Burkitt's, Hodgkin's, and posttransplant lymphomas) presumably are derived from GC B cells, EBV(+) GC B cells resembling these EBV(+) GC B cell lymphomas in terms of EBV gene expression and somatic hypermutation pattern could not be identified.
authors.affiliation: Institute for Genetics and Department of Internal Medicine I, University of Cologne, 50931 Cologne, Germany. Julia.Kurth@uni-koeln.de
authors.forename: Julia
authors.initials: J
authors.lastname: Kurth
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D015870:Gene Expression; D005814:Genes, Viral; D018858:Germinal Center / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D007244:Infectious Mononucleosis / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D016393:Lymphoma, B-Cell / Q000209:etiology; D008297:Male; D008969:Molecular Sequence Data
chemical_list: D004279:DNA, Viral