The effect of dose in tolerance induction on the subsequent response to a cross-reactive antigen.

The amount of antibody produced by BSA-tolerant rabbits as a result of immunization with DNP—BSA is dependent upon the amount of BSA used to induce tolerance. Tolerance was induced by initial injection of 100 μg of antigen followed by progressively higher doses. Rabbits rendered tolerant with a maximum BSA dose of 1 mg had a mean serum anti-BSA antibody concentration of 0.39 mg/ml after immunization with DNP—BSA, whereas rabbits rendered tolerant with a maximum BSA dose of 100 mg had a mean serum anti-BSA concentration of 0.02 mg after the same course of immunization. This compares with a mean of 1.08 mg of anti-BSA antibody in normal rabbits immunized with DNP—BSA. There was a similar reduction in the concentration of anti-DNP antibodies and of conjugate-specific antibodies in the tolerant groups. The results are discussed in terms of a thermodynamically-controlled induction of tolerance in individual precursor cells.