HUMAN-]MOUSE RADIATION CHIMERA DO NOT DEVELOP EPSTEIN-BARR-VIRUS LYMPHOMA

It has been shown that engraftment of human peripheral blood lymphocyt es (PBL) from Epstein-Barr virus (EBV) seropositive donors in C.B-17/S CID mice is associated with a high incidence of human B cell tumors. M ore recently, we described a new approach enabling engraftment of huma n PBL in normal strains of mice or rats receiving lethal split-dose ra diation and radioprotected with SCID bone marrow. We now demonstrate t hat, in contrast to SCID recipients of human PBL, Balb/c and C3H/HeJ r ecipients of 50-100 x 10(6) human PBL did not develop any EBV lymphoma during a 7-month follow-up period, but were successfully engrafted wi th human B and T cells. On the other hand, lymphoma developed in 90% o f the C.B-17/SCID mice infused with 70 x 10(6) human PBL from the same donor. Likewise, 36% of beige/nude/xid (BNX) mice, exposed to 12 Gy T BI, radioprotected with SCID bone marrow and then transplanted with hu man PBL developed lymphoma. Similar results were obtained when differe nt strains were infused with PBL of the same donor. Immunohistochemica l analysis indicated that the tumor cells were of human B cell origin and expressed the EBV-encoded latent membrane protein-1 and nuclear an tigen 2. While further studies are required to understand the mechanis ms which suppressed outgrowth of EBV lymphoma in human --> mouse radia tion chimera, compared to human --> C.B-17/SCID or human --> BNX chime ra, this marked resistance offers new possibilities for transplantatio n of hematopoietic tissues or cells from EBV-positive donors.