INDUCTION OF TOLERANCE TO HETEROLOGOUS PROTEINS AND THEIR CATABOLISM IN C57BL/6 MICE

Abstract

C57BL/6 mice were rendered tolerant to one or another of 13 soluble protein antigens. Tolerance was induced by a single injection of 20 mg protein within 24 hours after birth. The duration of the unresponsive state was measured and compared with the rates of catabolism of the antigens as determined in adult and new born mice. The data presented fail to show a correlation between the persistence of labeled protein antigen and the duration of tolerance. In several occasions, even an inverse relationship between duration of the unresponsive state and persistence was demonstrated. The results, therefore, strongly indicate that the duration of tolerance is not dependent on the rates of catabolism of the antigens. Several of the commercial protein preparations used in this study contained minor impurities to which the animals were generally not rendered tolerant. By means of diffusion in agar techniques, it was demonstrated that mice injected at birth with a tolerance-inducing dose of antigen would generally not reveal precipitating antibodies to this antigen after the tolerant state had been abolished. A speculative explanation was given in terms of quantitative or qualitative differences of antibodies found in such animals as compared to the immunized control mice. After the 3rd or 4th day of life, newborn mice catabolized I131-labeled heterologous proteins at the same rates as adult mice. The apparent slow elimination during the first days of life was, at least in part, the result of retention of nonprotein-bound I131.