EVIDENCE FOR TRANSFORMATION OF SPLEEN CELLS ONE DAY AFTER INFECTION OF MICE WITH FRIEND LEUKEMIA VIRUS : AUTONOMOUS GROWTH POTENTIAL AND EXPRESSION OF HYBRID-RESISTANCE GENES

Proliferation and erythroid differentiation of transplanted DBA/2 marrow cells and Friend virus-induced leukemic cells were assessed in syngeneic, allogeneic (H-2 compatible), and (BALB/c x DBA/2)F(1) hybrid mice (CDF(1)). Measurements were made 5 days after transplantation of donor cells into nonirradiated or X-irradiated mice by the spleen colony or the (125)IUdR-(59)Fe uptake methods. Growth of DBA/2J (Jackson subline) marrow grafts was poor in irradiated CDF(1)J hybrids as compared with growth in syngeneic and allogeneic hosts. The DBA/2J transplants proliferated, however, without impairment in irradiated CDF(1) hybrids which were the progeny of DBA/2 male parents of other sublines, e.g. DBA/2Ha, DBA/2Cr, and DBA/2Cum. In contrast, tissue-cultured Friend leukemic cells of DBA/2J origin grew deficiently in all CDF(1) hybrids tested, regardless of irradiation and of the DBA/2 parent's subline. The growth pattern of transplanted DBA/2J cells was a manifestation of hybrid resistance. The results with DBA/2J and other DBA/2 subline grafts suggested that hybrid histocompatibility alleles were expressed to a greater extent in leukemic than in normal marrow cells, for the former were consistently recognized as "nonself" by CDF(1) mice, but not the latter cells. The property of deficient growth in irradiated CDF(1)Ha hybrids was acquired by DBA/2J hemopoietic cells within 6 hr from infection in vivo with Friend leukemia virus, and persisted during the following 8 days. It was ascribed to enhanced expression of hybrid histocompatibility gene(s) (Hh) induced by the virus. Autonomous growth potential of hemopoietic cells, manifested by proliferation in nonirradiated recipients, was first detected 24 hr from infection, and likewise persisted at the later intervals. At the same time, the infected cells grew deficiently also in nonirradiated CDF(1)Ha mice. The two irreversible cellular changes were regarded as the earliest signals of virus-induced transformation.