Epstein-Barr virus induces aggressive lymphoproliferative disorders of human B cell origin in SCID/hu chimeric mice.
C.B-17 scid mice were reconstituted by intraperitoneal injection of human tonsil cells or PBL from EBV-seronegative donors. Subsequent injection of EBV resulted in the rapid development (within 19-33 d) of aggressive, fatal, lymphoproliferative disorders of human B cell origin. Autopsies revealed solid tumors in the abdomen, and occasionally in the liver, thymus, or spleen. Histopathologic analysis showed that the tumors were high-grade immunoblastic lymphomas and FACS analyses of tumor cells indicated that they were of human B-lymphoid origin. The tumor cells grew in vitro and induced new tumors on injection into severe combined immunodeficient (SCID) mice. Karyotypic analysis and Southern blots for c-myc or bcl-2 rearrangements revealed no chromosomal abnormalities and translocations. Southern blot analysis also showed that the cells possessed EBV DNA sequences. Although these tumors undoubtedly reflect infection of the transferred B cells with EBV in vivo, intraperitoneal transfer of short-term lymphoid cell lines transformed in vitro with EBV resulted in ascites production without evidence of tumor formation.
Cannon
M J
MJ
Research Institute of Scripps Clinic, Department of Immunology, La Jolla, California 92037.
Pisa
P
P
Fox
R I
RI
Cooper
N R
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D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes; D002678:Chimera; D004195:Disease Models, Animal; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications*; D007621:Karyotyping; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D009368:Neoplasm Transplantation
D015703:Antigens, CD