immunity to AKR leukemia (Ir genes/T cells/humoral responsiveness/H-2-linked loci/tumor

This paper provides evidence for the involve- ment of immune mechanisms in conferring resistance to a spontaneous AKR leukemia. It is shown that genes in the B, J, or E subregions of the H-2 complex confer resistance to a spontaneously arisen, tissue culture-adapted AKR thymoma, BW5147. A direct correlation is demonstrated between survival to injected BW5147 cells and humoral responsiveness in various hybrids obtained from crosses of AKR mice and C57BL/10 or C3H/DiSn derived congeneic strains differing at H-2. Cellular immunity appears to play no role in resistance to the prolifer- ation of tumor cells. It is further established that development of effective humoral immunity depends on B cells and Ly-l+, 2-, 3- helper T-cells bearing the I-Jk phenotype. These findings seem directly applicable to the spontaneous disease, and results of studies using transformed cells from an overtly leukemic AKR mouse parallel those obtained using BW1547 cells. The involvement of the major histocompatibility complex, H-2, in resistance or susceptibility to virus-induced leukemogenesis was first demonstrated experimentally by Lilly and his co- workers (1) and subsequently extended by numerous investi- gators (2). The mechanisms of action of H-2-linked loci in disease associations are unknown. Some investigators (3-7) have suggested that H-2-linked resistance to virus-induced leuke- mogenesis may result from genetically controlled variation in immune responses to virus-induced antigens (8). The present communication provides evidence for the involvement of im- mune mechanisms in conferring resistance to a spontaneous AKR leukemia and defines the humoral response involved, including the involvement of an I-J+, Ly-1+, 2-, 3- T cell.