Immunologic Tolerance Induced in the Adult Rabbit with Modified BSA

Summary Previous experiments have shown that bovine serum albumin, cleared of its larger phagocytizable particles, is much less immunogenic than regular BSA and can sometimes induce tolerance. These findings are confirmed in the present paper. It was also shown that 1 mg of BSA was the dose most likely to induce tolerance in the rabbit; a smaller proportion of tolerant animals was obtained with 7 mg, whereas no tolerance was obtained with 25 mg of the antigen. The 0.1-mg dose induced slightly less tolerance than 1 mg, but the difference was not significant. In most experiments the antigen was screened by injection into a filter animal before injection into experimental animals. In some experiments this biologic filtration was replaced by gel filtration, which also allowed the separation of a “tolerigen” fraction from an immunogenic one. The immunogenic role of the larger component is probably related to its function of adjuvant, since screened BSA injected together with endotoxin is immunogenic and can no longer induce tolerance. The specificity of this kind of tolerance was established by showing a normal immune response to HSA in rabbits tolerant to BSA. This state of tolerance may persist for several months—one animal has now been tolerant for more than 2 years.