LYMPHOPROLIFERATIVE DISEASE IN HUMAN PERIPHERAL-BLOOD-MONONUCLEAR-CELL-INJECTED SCID MICE .2. ROLE OF HOST AND DONOR FACTORS IN TUMOR GENERATION

Intraperitoneal injection of lymphoid cells from EBV(+) donors into SC ID mice might provide a useful tool for studying the pathways of B-cel l lymphomagenesis in man. Since previous studies showed that donor T c ells greatly favor B-cell proliferation and tumor generation in this m odel, we addressed the host and donor factors involved in limiting or promoting lymphoma development. The number of EBV-infected B-cell prec ursors was crucial, since purified B lymphocytes, which alone were una ble to generate tumors, underwent expansion and established tumor mass es when the animals were inoculated with an EBV-containing supernatant . Host factors were critical in limiting tumor development; in vivo NK -cell removal allowed purified B cells to expand and proceed to tumors in the absence of T lymphocytes, whereas potentiation of mouse NK-cel l activity prevented tumor generation in PBMC- and LCL-injected animal s. The T-cell-derived factors that favor lymphomagenesis could not be identified; IL-2, IL-4, IL-6, and soluble CD23 were not able to promot e B-cell expansion, and treatment of PBMC-injected mice with the relev ant anti-cytokine anti-sera did not counteract lymphoma development. T hese experiments also showed that IL-6 plays a minor role, if any, in B-cell lymphoproliferation in this model. Our data indicate that recon stitution of SCID mice with PBMC from EBV(+) donors may constitute a u seful model for determining the events involved in lymphomagenesis in humans, provided that strict control of all the experimental variables is guaranteed. (C) 1994 Wiley-Liss, Inc.