Immunologic induction of reticulum cell sarcoma: donor-type lymphomas in the graft-versus-host model

The aim of this study was to investigate malignant lymphomas of donor origin induced in F1 mice undergoing a chronic graft-versus-host reaction (GVHR) after injection of parental strain spleen cells. A total of 3 X 10(8) or 4 X 10(8) C57BL/10 spleen cells were administered to 7-8-week-old H-2 incompatible (C57BL/10 X HTG)F1 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 F1 mice, cells failed to be killed by a hyperimmune serum against HTG (H-2g) but reacted normally with antisera to C57BL/10 (H-2b) 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 animals lacked immunoglobulins bearing host-derived Iga allotype in their serum. Forty-three percent of the GVH F1 mice developed reticulum cell sarcomas (RCS), 32% revealed hyperplastic lymphoreticular tissue, and 25% showed no grossly abnormal changes. Mice with donor-type lymphoid 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).