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, tumors developed in association with high levels of human Ig in mouse serum and detectable IL-6 levels. The tumors showed a histopathologic pattern reminiscent of large cell immunoblastic non-Hodgkin's lymphoma; in situ hybridization invariably evidenced EBV sequences in a minority of cells. Genotypic analysis of tumors arising in PBMC-injected mice showed the presence of different oligoclonal B cell populations in different tumor sites. Southern blot analysis disclosed the presence of both linear (replicating) and episomal (latent) EBV DNA forms; sequential analysis of LCL cells serially passaged into animals revealed the progressive selection of clonal cells with only the latent episomal form. Attempts to dissect the events underlying tumor development revealed that the presence of T cells within the injected population was essential for tumor generation; however, the putative T cell-derived factors involved are unclear, and IL-6 seems to play a minor role.