PROPERTIES OF TUMORS ARISING IN SCID MICE INJECTED WITH PBMC FROM EBV-POSITIVE DONORS

Groups of SCID mice were injected with different PBMC sub-populations, and established LCL cells. In about 80% of PBMC-injected animals, tum ors developed in association with high levels of human Ig in mouse ser um and detectable IL-6 levels. The tumors showed a histopathologic pat tern reminiscent of large cell im-munoblastic non-Hodgkin's lym-phoma; in situ hybridization invariably evidenced EBV sequences in a minorit y of cells. Genotypic analysis of tumors arising in PBMC-injected mice showed the presence of different oligoclonal B cell populations in di fferent tumor sites. Southern blot analysis disclosed the presence of both linear (replicating) and episomal (latent) EBV DNA forms; sequent ial analysis of LCL cells serially passaged into animals revealed the pro-gressive selection of clonal cells with only the latent episomal f orm. Attempts to dissect the events under-lying tumor development reve aled that the presence of T cells within the injected population was e ssential for tumor generation; however, the putative T cell-derived fa ctors involved are unclear, and IL-6 seems to play a minor role.