ABSTRACT
This chapter aims to explore the work that provided the unambiguous evidence for systematic changes in the affinity of antibodies synthesized in response to a single antigenic determinant. The impact of the work derives in large measure from two considerations. First, it provides a clear functional correlate for the somatic mutations that occur in the rearranged immunoglobulin V genes of B lymphocytes. The second consideration is a matter of historical timing. Antibodies isolated from early samples of antiserum had low intrinsic affinity for the homologous hapten, and those isolated from later samples had progressively increasing intrinsic affinity for the same hapten. The realization that the newly generated antibodies had extraordinarily high affinity grew out of studies carried out with Sidney Velick and Charles Parker. The average affinity of serum antibodies only appears to increase because of changes in the levels of the injected antigen.
