Heterogeneity among Epstein-Barr virus-seropositive donors in the generation of immunoblastic B-cell lymphomas in SCID mice receiving human peripheral blood leukocyte grafts.
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 (greater than 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-sero-positive 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.
Picchio
G R
GR
Division of Immunology, Medical Biology Institute, La Jolla, California 92037.
Kobayashi
R
R
Kirven
M
M
Baird
S M
SM
Kipps
T J
TJ
Mosier
D E
DE
D000367:Age Factors; D000818:Animals; D004261:DNA Replication; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000502:physiology; D006801:Humans; D015994:Incidence; D017708:Leukocyte Transfusion; D007962:Leukocytes / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000453:epidemiology / Q000209:etiology*; D051379:Mice; D016513:Mice, SCID; D010641:Phenotype; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000209:etiology*; D014779:Virus Replication