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* Department of Pathology, Jaharis Building, Tufts University School of Medicine, Boston, MA 02111;
Department of Biochemistry, Tufts University School of Medicine, Boston, MA 02111; and
Pediatrics and Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
Peripheral blood memory B cells latently infected with EBV bear somatic mutations and are typically isotype switched consistent with being classical Ag-selected memory B cells. In this work, we performed a comparative analysis of the expressed Ig genes between large sets of EBV-infected and uninfected peripheral blood B cells, isolated from the same infectious mononucleosis patients, to determine whether differences exist that could reveal the influence of EBV on the production and maintenance of these cells. We observed that EBV+ cells on average accumulated more somatic hypermutations than EBV– cells. In addition, they had more replacement mutations and a higher replacement-silent ratio of mutations in their CDRs. We also found that EBV occupies a skewed niche within the memory compartment, due to its exclusion from the CD27+IgD+IgM+ subset, but this skewing does not affect the overall structure of the compartment. These results indicate that EBV impacts the mutation and selection process of infected cells but that once they enter memory they cannot be distinguished from uninfected cells by host homeostasis mechanisms.
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1 This work was supported by United States Public Health Research Grants CA65883, AI18757, and AI062989 (to D.T.L.) and AI49320 (to K.L.).
2 Address correspondence and reprint requests to Dr. David A. Thorley-Lawson, Department of Pathology, Jaharis Building, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111. E-mail address: david.thorley-lawson{at}tufts.edu
3 Abbreviations used in this paper: CSR, class switch recombination; EBER, EBV-encoded RNA; FWR, framework region; GC, germinal center; IM, infectious mononucleosis; LMP, latent membrane protein; R, replacement; S, silent; SHM, somatic hypermutation; PB, peripheral blood.
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