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Epstein-Barr virus induced lymphoproliferative tumors in severe combined
immunodeficient mice are oligoclonal
P Pisa, MJ Cannon, EK Pisa, NR Cooper and RI Fox
Department of Immunology, Scripps Clinic and Research Foundation, La Jolla,
CA 92037.
Severe combined immunodeficient (SCID) mice reconstituted with lymphocytes
from Epstein-Barr virus (EBV) negative human donors develop aggressive
tumors after the chimeric mice are infected with EBV. The tumors were
composed of human B cells that expressed EBV encoded antigens (latent
membrane protein and EBV nuclear antigen2). Southern blot analysis of DNA
from 16 SCID/hu tumors with human Ig gene probes showed that each tumor
contained multiple heavy and light chain gene rearrangements. Ig kappa gene
rearrangements were frequent, while clonal lambda gene rearrangements were
infrequent. Analysis of EBV terminal repeat sequences indicated two or more
fused termini in each tumor, consistent with a multiclonal origin. Linear
terminal repeat segments and viral antigens (EA-D and EA-R) associated with
EBV replication were not detected in the tumors. High levels of human Igs
in the SCID/hu serum were oligoclonal and primarily contained kappa light
chains. Before the appearance of overt tumors, circulating cells with human
and EBV DNA could be detected in the SCID/hu mice by the polymerase chain
reaction. We conclude that EBV infection in SCID/hu chimeric mice produces
a limited number of transformation events, which give rise to oligoclonal
tumors resembling EBV-associated lymphoproliferative disorders in some
immune-deficient patients.
Volume 79,
Issue 1,
pp. 173-179,
01/01/1992
Copyright © 1992 by The American Society of Hematology
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