Department of Pediatrics; Program in Molecular Medicine
Adolescent; Adult; B-Lymphocytes; Base Sequence; DNA Primers; DNA, Complementary; Flow Cytometry; Genes, Immunoglobulin; *Herpesvirus 4, Human; Humans; Immunologic Memory; Infectious Mononucleosis; Molecular Sequence Data; Mutation; Sequence Analysis, DNA
Immunology and Infectious Disease | Pediatrics
Epstein-Barr virus (EBV) establishes a lifelong persistent infection within peripheral blood B cells with the surface phenotype of memory cells. To date there is no proof that these cells have the genotype of true germinal-center-derived memory B cells. It is critical to understand the relative contribution of viral mimicry versus antigen signaling to the production of these cells because EBV encodes proteins that can affect the surface phenotype of infected cells and provide both T cell help and B cell receptor signals in the absence of cognate antigen. To address these questions we have developed a technique to identify single EBV-infected cells in the peripheral blood and examine their expressed Ig genes. The genes were all isotype-switched and somatically mutated. Furthermore, the mutations do not cause stop codons and display the pattern expected for antigen-selected memory cells based on their frequency, type, and location within the Ig gene. We conclude that latently infected peripheral blood B cells display the molecular hallmarks of classical antigen-selected memory B cells. Therefore, EBV does not disrupt the normal processing of latently infected cells into memory, and deviations from normal B cell biology are not tolerated in the infected cells. This article provides definitive evidence that EBV in the peripheral blood persists in true memory B cells.
Rights and Permissions
Copyright © 2005, The National Academy of Sciences. Freely available online through the PNAS open access option.
DOI of Published Version
Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18093-8. Epub 2005 Dec 5. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Souza, Tatyana A.; Stollar, B. David; Sullivan, John L.; Luzuriaga, Katherine; and Thorley-Lawson, David A., "Peripheral B cells latently infected with Epstein-Barr virus display molecular hallmarks of classical antigen-selected memory B cells" (2005). Immunology/Infectious Disease. 45.