Lymphoproliferative disease in human peripheral-blood-mononuclear-cell-injected scid mice. II. Role of host and donor factors in tumor generation

✍ Scribed by Arianna Veronesi; Vincenzo Coppola; Maria Luisa Veronese; Chiara Menin; Laura Bruni; Emma D'Andrea1; Marta Mion; Alberto Amadori; Luigi Chieco-Bianchi

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: French
• Weight: 960 KB
• Volume: 59
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910590516

✦ Synopsis

lntraperitoneal injection of lymphoid cells from EBV+ donors into SCID mice might provide a useful tool for studying the pathways of B-cell lymphomagenesis in man. Since previous studies showed that donor T cells greatly favor B-cell proliferation and tumor generation in this model, we addressed the host and donor factors involved in limiting or promoting lymphoma development. The number of EBV-infected B-cell precursors was crucial, since purified B lymphocytes, which alone were unable to generate tumors, underwent expansion and established tumor masses 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-cell activity prevented tumor generation in PBMC-and LCL-injected animals. 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 promote B-cell expansion, and treatment of PBMCinjected mice with the relevant anti-cytokine anti-sera did not counteract lymphoma development. These experiments also showed that IL-6 plays a minor role, if any, in B-cell lymphoproliferation in this model. Our data indicate that reconstitution of SCID mice with PBMC from EBV+ donors may constitute a useful model for determining the events involved in lymphomagenesis in humans, provided that strict control of all the experimental variables is guaranteed.