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.
Veronesi
A
A
Institute of Oncology, Interuniversity Center for Research on Cancer, University of Padua, Italy.
Coppola
V
V
Veronese
M L
ML
Menin
C
C
Bruni
L
L
D'Andrea
E
E
Mion
M
M
Amadori
A
A
Chieco-Bianchi
L
L
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