Epstein-Barr Virus–infected Resting Memory B Cells, not Proliferating Lymphoblasts, Accumulate in the Peripheral Blood of Immunosuppressed Patients

doi:10.1084/jem.190.4.567

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J. Exp. Med., Volume 190, Number 4, August 16, 1999 567-576
Copyright © 1999 by The Rockefeller University Press.

Epstein-Barr Virus–infected Resting Memory B Cells, not Proliferating Lymphoblasts, Accumulate in the Peripheral Blood of Immunosuppressed Patients

Gregory J. Babcock^a, Lisa L. Decker^a, Richard B. Freeman^b, and David A. Thorley-Lawson^a
^a From the Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111
^b Division of Transplant Surgery, New England Medical Center Hospitals, Boston, Massachusetts 02111

Correspondence to: David A. Thorley-Lawson, Department of Pathology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111. Tel:617-636-2726 Fax:617-636-2990 E-mail:dlawson{at}opal.tufts.edu.

When Epstein-Barr virus (EBV) infects B cells in vitro, theresult is a proliferating lymphoblast that expresses at leastnine latent proteins. It is generally believed that these cellsare rigorously controlled in vivo by cytotoxic T cells. Consistentwith this, the latently infected cells in the peripheral bloodof healthy carriers are not lymphoblasts. Rather, they are restingmemory B cells that are probably not subject to direct immunosurveillanceby cytotoxic T lymphocytes (CTLs). When patients become immunosuppressed,the viral load increases in the peripheral blood. The expansionof proliferating lymphoblasts due to the suppressed CTL responseis believed to account for this increase and is considered tobe a major risk factor for posttransplant lymphoproliferativedisease (PTLD) and AIDS-associated B cell lymphoma. Here weshow that there is an increase in the numbers of latently infectedcells in the peripheral blood of immunosuppressed patients.However, the cells are not proliferating lymphoblasts. Theyare all latently infected, resting, memory B cells—thesame population of infected cells found in the blood of healthycarriers. These results are discussed in the context of a modelfor EBV persistence that explains why PTLD is usually limitedto the lymph nodes.

Key Words: Epstein-Barr virus, B cell, latency, immunosuppression

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