Decreasing antigen in vivo may preferentially stimulate cells with the potential for synthesis of high-affinity antibody through activation of surface receptors with similarly high affinity. This selection should result in cells with increased sensitivity to lower antigen concentrations, cells with greater avidity for antigen. We have followed the in vivo changes in anti-TNP memory-cell sensitivity by initiating the secondary anti-hapten response in vitro. This response was determined by anti-TNP plaque assay. The results indicate that cell populations with increased sensitivity for antigen continue to emerge with time after priming and that this sensitivity may increase 1000-fold in a 4 month period. Increased sensitivity to stimulation by antigen is concomitant with suppression by higher, previously stimulatory doses as in high zone immune tolerance. The data support the hypothesis that memory cells of high avidity result from the selective pressure of diminishing in vivo antigen concentration.

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