Immunologic induction of reticulum cell sarcoma: donor‐type lymhomas in the graft‐versus‐host model

The aim of this study was to investigate malignant lymphomas of donor origin induced in F 1 mice undergoing a chronic graft‐versus‐host reaction (GVHR) after injection of parental strain spleen cells. A total of 3 × 10 8 or 4 × 10 8 C57BL/10 spleen cells were administered to 7—8‐week‐old H‐2 incompaltible (C57BL/10 × HTG)F 1 hybrids either as single or fractionated i.p. injections. Recipients were killed at intervals ranging from 1 month to 1 year after the first injection and their lymphoid cells typed for host‐derived and donor‐derived histocompatibility antigens. In 49 % of the 88 GVH F 1 mice, cells failed to be killed by a hyperimmune serum against HTG (H‐2 g ) but reacted normally with antisera to C57BL/10(H‐2 b ) and, in the 9 cases tested, to theta‐C3H. The conclusion that the lymphoid cells of these mice were derived from donor cells was supported by the finding that these amimals lacked immunoglobulins bearing host‐derived Ig a allotype in their serum. Forty‐three percent of the GVH F 1 mice developed reticulum cell sarcomas (RCS), 32 % revealed hyperplasticlymphoreticular tissue, and 25 % showed no grossly abnormal changes. Mice with donor‐typelymphoid tissues were found in all three groups; 50 % of the 38 RCS detected were donor‐type neoplasms. The induction of donor‐type RCS during the GVHR strengthens the concept of lymphomagenesis through persistent stimulation with antigen(s).