The clonal origin of cells contributing to successive phases of a cyclical immune response

A single injection of mice with a low dose of sheep red blood cells results in a cyclic appearance of antibody-forming cells of the IgG classes. The peaks of the responses occur at the same time in the spleen and the thoracic lymph nodes. We have investigated the phenomenon with respect to IgG2a response by using the isoelectric focusing overlay assay and have assumed that in the great majority of cases, after immunization with limiting amounts of antigen, an individual spectrotype represents a "clonal" product. Enumeration of spectrotypes which arise only in the first peak and those which arise only in the second, suggests that the second peak of plaque-forming cells can be accounted for on the basis of the stimulation of a second population of precursor cells. Several possible mechanisms whereby new antigen-sensitive precursor cells can be turned on late in a primary response are discussed.