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Heterogeneity among Epstein-Barr Virus-seropositive Donors in the Generation of Immunoblastic B-Cell Lymphomas in SCID Mice Receiving Human Peripheral Blood Leukocyte Grafts¹

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

Epstein-Barr virus (EBV) is associated with B-cell malignancy in immunosuppressed humans and SCID mice receiving human peripheral blood leukocyte grafts (hu-PBL-SCID). We have further characterized the process of lymphoma development in hu-PBL-SCID mice. We report that EBV-seropositive donors differ markedly in the capacity of their PBL to give rise to immunoblastic lymphomas in SCID mice; some donors (high incidence) generated tumors rapidly in all hu-PBL-SCID mice, other donors (intermediate-low incidence) gave rise to sporadic tumors after a longer latent period (>10 weeks), and some donors failed to produce tumors. B-cell lymphomas arising from high incidence donors were multiclonal in origin, and EBV replication was detected in all tumors. Tumors derived from intermediate-low incidence donors were monoclonal or oligoclonal and often had no evidence of viral replication. All tumors, regardless of the donor, resembled EBV-transformed lymphoblastoid cell lines in surface phenotype but differed from lymphoblastoid cell lines by having less Epstein-Barr nuclear antigen 2 and CD23 expression. The variable patterns of lymphomagenesis seen among different EBV-seropositive donors may be explained by lower levels of specific immunity to EBV in high incidence donors, permitting activation of EBV replication and potential transformation of secondary B-cell targets. In addition, there may be differences in the transforming potential of EBV infecting different donors. The use of the hu-PBL-SCID model may help predict patients at high risk for posttransplant or acquired immunodeficiency syndrome-associated lymphomas.

¹ This work was supported by NIH Grants AI-29182, AI-22871, AI-24526, and CA-54755. This is Manuscript 222 from the Medical Biology Institute.

² To whom requests for reprints should be addressed.

Received 11/25/91. Accepted 2/26/92.

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