Hapten-carrier relationships in immunological unresponsiveness. II. Decrease of antibody affinity and specificity in B cell tolerance.

Mice were rendered tolerant to a haptenic determinant NIP by cyclophosphamide treatment and subsequent multiple intraperitoneal injections of NIP coupled to mouse serum albumin. Control mice received no antigen. The mice were challenged with immunogenic NIP-conjugates 20 days after stopping the tolerance inducing treatment. The response to the hapten was reduced, while the response to the carrier was normal. A second challenge showed absence of memory cell development towards the hapten. To study antibody affinity in tolerance rats were rendered tolerant to NNP-human serum albumin and challenged later with the tolerogen. The rats developed very little anti-NNP antibodies until 3 months after the tolerance inducing treatment. Then the affinity of antibodies was low in the tolerant group. A partial tolerance lasted one year, which is remarkably long when compared to other works on the length of B cell tolerance. Tolerant animals had only weakly specific antibody to the tolerogen in contrast to the controls. Maturation of antibody affinity was paralleled by increase in specificity in the control rats.