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

Mice with severe combined immunodeficiency were inoculated intraperitoneally with 50 x 10(6) 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 poly-oligo- 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.