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Epstein-Barr Virus-induced Human B-Cell Lymphomas in SCID Mice Reconstituted with Human Peripheral Blood Leukocytes¹

Medical Biology Institute, La Jolla, California 92037 [D. E. M., G. R. P.], and University of California, San Diego, San Diego, California 92093-0663 [S. M. B., R. K., T. J. K.]

Epstein-Barr virus (EBV) infection is associated with immunoblastic B-cell lymphomas in immunosuppressed or human immunodeficiency virus-infected individuals and in SCID mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID) from EBV-seropositive donors. The risk of tumors appearing in the hu-PBL-SCID mice differs among EBV-seropositive donors. Four different outcomes have been noted: (a) no tumors appear (no incidence donors); (b) tumors appear in a fraction of hu-PBL-SCID mice with a 10–20 week latent period (low- and intermediate-incidence donors); or (c) tumors appear in all hu-PBL-SCID mice within 6–10 weeks (high-incidence donors). The latter category of rapidly appearing tumor invariably involved activation of EBV replication, whereas more slowly growing tumors rarely activated EBV. The results indicate that prospective screening of high-risk individuals in the hu-PBL-SCID model may predict the risk of EBV-associated lymphoma development.