ISOLATION OF ANTIGEN-BINDING CELLS FROM UNPRIMED MICE Demonstration of Antibody-Forming Cell Precursor Activity and Correlation between Precursor and Secreted Antibody Avidities* BY MICHAEL H. JULIUS AND LEONARD

The time-dependent increase in the average affinity of serum antibody after immunization (1), is said to be a result of antigen-driven selection of those antibody-forming cell precursors having the highest affinity antigen receptors (2). This interpretation infers that the specificity and affinity of antigen-binding receptors on antibody-forming cell precursors are directly correlated to the serum antibody produced by progeny antibodysecreting cells. It has been found that changes in the affinity of serum antibody with time after immunization reflect changes in the population of antibody-secreting cells. By determining the concentration of antigen required to inhibit individual plaque-forming cells (PFC) assayed at various times after immunization, a time-dependent avidity increase at the antibody-secreting cell level is seen and is comparable to the increase in affinity found in serum antibody (3). Thus, a good correlation between the (intrinsic) affinity of serum antibody and the avidity of the antibody-secreting cell products has been established. In contradistinction, evidence correlating the avidity of antigen receptors on antibodysecreting cell precursors, with the avidity of antibody secreted by their progeny cells, is meager. Indirect evidence has been reported demonstrating that memory cells with high avidity antigen-binding receptors are required to give rise to high avidity antibody-secreting cells (4). However, the putatively high avidity precursors were not isolated and tested directly in these experiments.