Lymphoproliferative disease in human peripheral-blood-mononuclear-cell- injected scid mice. II. Role of host and donor factors in tumor generation.
Intraperitoneal 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 PBMC-injected 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.
Institute of Oncology, Interuniversity Center for Research on Cancer, University of Padua, Italy.
A
A
Veronesi
V
V
Coppola
M L
ML
Veronese
C
C
Menin
L
L
Bruni
E
E
D'Andrea
M
M
Mion
A
A
Amadori
L
L
Chieco-Bianchi
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001402:B-Lymphocytes / Q000473:pathology / Q000637:transplantation* / Q000821:virology; D001483:Base Sequence; D002469:Cell Separation; D004279:DNA, Viral / Q000032:analysis; D005677:G(M1) Ganglioside / Q000037:antagonists & inhibitors / Q000502:physiology; D015321:Gene Rearrangement; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000473:pathology / Q000637:transplantation*; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000821:virology; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D000906:Antibodies; D004279:DNA, Viral; D015850:Interleukin-6; D005677:G(M1) Ganglioside