Genetics of natural antitumor antibody production: antibodies to MHC-linked determinants detected in the serum of unstimulated mice.

The genetics of natural antitumor antibodies was studied in several murine strains with 4 target tumors. We found that the levels of NAb detected depended on the strain-tumor combination and that high levels of NAb were inherited recessively. These observations suggested that NAb specificities are selectively regulated. Studies of backcross progeny and of H-2 congenic mice provided evidence for the genetic linkage between NAb levels and the MHC. From studies in which it was demonstrated that allogeneic NAb were absorbed with splenocytes bearing the haplotype of the target cell but not by other splenocytes, it was concluded that allo-NAb were recognizing H-2 antigenic determinants, or an antigen(s) whose expression is closely linked to the MHC. It is suggested, therefore, that low levels of NAb against the DBA/2 tumors studied in mice of the d haplotype were due to self tolerance.