ENGRAFTMENT OF HUMAN NON-HODGKIN LYMPHOMAS IN MICE WITH SEVERE COMBINED IMMUNODEFICIENCY

Background. Malignant non-Hodgkin lymphoma (NHL) is one of the most di fficult neoplasms to transplant into nude mice. Mice with severe combi ned immunodeficiency (SCID) accept various human cancers much more eff iciently than do nude mice. The authors investigated whether SCID mice could be used as convenient hosts in which to grow human NHL in vivo. Methods. Fifty NHL specimens were engrafted into SCID mice. The origi nal specimens and the tumors that developed in SCID mice were studied immunohistologically and by Southern blot analysis to clarify their cl onal identity and to determine if they were Epstein-Barr virus (EBV)-t ransformed B cell proliferations.Results. SCID tumors developed from 2 3 of 50 NHL specimens. Ten tumors were identical immunophenotypically and, partly, genotypically to the original NHL, showing that the origi nal NHL grew in the SCID mice. B-cell NHL rather than T-cell NHL and h igh-grade rather than low-grade malignancy groups were much more easil y heterotransplanted. Most of the heterotransplanted NHL were maintain ed by successive transplantation. In two other SCID tumors, the origin al NHL clones and a newly developed B-cell clone coexisted. The remain ing 11 SCID tumors were composed of newly developed clones. The latter 13 tumors were shown to be human cells of B-cell lineage bearing EBV latent proteins-latent membrane protein 1 and EB nuclear antigen 2-sug gesting that they originated from EBV-infected B-cells that were prese nt in the original tumor tissues. Conclusion. SCID mice accept human N HL far more efficiently than do nude mice. However, frequent occurrenc e of spontaneous EBV-associated B-cell proliferation must be kept in m ind.