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Role of Epstein-Barr virus and interleukin 6 in the development of lymphomas of human origin in SCID mice engrafted with human tonsillar mononuclear cells

¹ Department of Pediatrics
² Department of Microbiology
and³ Department of Otolaryngology, State University of New York at Buffalo School of Medicine and Biomedical Sciences, and Children's Hospital of Buffalo, Buffalo, New York 14222
and⁴ Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas 77550, U.S.A.

Mice with severe combined immunodeficiency were inoculated intraperitoneally with 50 x 10⁶ human tonsillar mononuclear cells (hu-TMCs) from Epstein-Barr virus (EBV) antibody seropositive or seronegative human subjects. Between 5 and 11 weeks later, 29.4% (10/34) of mice injected with hu-TMCs from EBV seropositive donors, but none of 34 animals receiving hu-TMCs from EBV seronegative donors, developed intraabdominal and/or intrathoracic tumours (P, 0.002). By means of in situ hybridization using alpha satellite DNA from human chromosome 17, all tumours produced after cell transfer from EBV seropositive donors were identified to be of human origin. Histologically the tumours resembled large cell lymphomas; the EBV genome was detected by in situ hybridization and EBV nuclear antigen by immunofluorescence in these tumours. The tumours were poly- or oligoclonal, and stained for human IgG and IgM, and less frequently IgA and IgD. Serum levels of human immunoglobulin in animals developing human tumours were significantly higher than in reconstituted mice without tumours and the sera exhibited polyoligo- or monoclonality in immunoelectrophoresis. Human interleukin 6 was detected in the serum of six of 10 animals with human lymphomas, but not in any animals without human lymphoma.

Received 1 July 1991; accepted 28 August 1991.