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PMID: 12665622 Published · ppublish English Case Reports Journal Article Research Support, Non-U.S. Gov't

Epstein-Barr virus-infected B cells expanding in germinal centers of infectious mononucleosis patients do not participate in the germinal center reaction.

Kurth J, Hansmann ML, Rajewsky K, Küppers R

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.

MeSH Terms
Adolescent Adult B-Lymphocytes/immunology,pathology,virology Base Sequence DNA, Viral/genetics,isolation & purification Gene Expression Genes, Viral Germinal Center/immunology,pathology,virology Herpesvirus 4, Human/genetics,immunology,pathogenicity Humans Infectious Mononucleosis/immunology,pathology,virology Lymphoma, B-Cell/etiology Male Molecular Sequence Data
Chemicals
DNA, Viral
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kurth Julia
Institute for Genetics and Department of Internal Medicine I, University of Cologne, 50931 Cologne, Germany. Julia.Kurth@uni-koeln.de
Hansmann Martin-Leo
Rajewsky Klaus
Küppers Ralf
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2003-04-15
Epub
2003-00-28
Pages
4730-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC153624
Subset
IM
Databases
GENBANK
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