A model for the mechanism of antibody induction and tolerance, with specific attention to the affinity characteristics of antibodies produced during the immune response.

The model for antibody induction and tolerance which is presented here is based on the premise that the interaction between antigen and a cell-bound, antibody-like receptor is crucial for the immune response. Activation and suppression of immunocompetent cells are determined by specific configurations of bound antigen on the cell surface. It is further postulated that the affinity of antibody produced by a given cell is a function of the number of receptor sites possessed by that cell. The theory was designed to account for the phenomena of high and low zone tolerance, and to explain the variations of antibody affinity observed during the immune response. In addition, it is found to be consistent with other experimental observations such as (1) the initial appearance of low affinity antibody in recovery from high zone tolerance, (2) the appearance of tolerance rapidly in vitro, and over a range of antigen doses which is relatively uniform for different antigens, and (3) the spontaneous passage of competent cells through a zone of activation on recovery from (high zone) tolerance. Moreover, the theory provides a number of testable predictions such as (1) a stimulatory effect of low doses of haptens on antibody induction by antigen, (2) an initial appearance of high affinity antibody on recovery from low zone tolerance, and (3) the correlation of cell-antigen affinity with antibody-antigen affinity. In addition, one could explore experimentally the propositions that the same cell is involved in antibody induction and tolerance, and that the number of receptor sites on cells of a given immunologic specificity may vary.