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Studies on the control of antibody synthesis. V. Effect of nonspecific modification of the magnitude of the immune response on the affinity of the antibody synthesized.

A progressive increase in antibody affinity occurred after immunization with dinitrophenylated keyhole limpet hemocyanin i.v. in the absence of adjuvants, provided a relatively low dose of antigen was used. When a higher dose of antigen was given i.v., very low affinity antibody was formed and no increase in affinity was observed. It is suggested that a high dose of antigen may stimulate lower affinity antibody-forming cells and induce tolerance in high affinity B lymphocytes. Adjuvants (complete Freund9s adjuvant and endotoxin) increased the magnitude of the response and slightly increased the rate of increase in affinity. Depression of antibody synthesis with 6-MP had no effect on affinity unless treatment was begun before immunization. Under these conditions a marked depression in the magnitude of the immune response and a slight decrease in affinity was observed. Thus, nonspecific modifications of the magnitude of the immune response with adjuvants or cytotoxic drugs can affect, but only slightly, the affinity of the antibody produced. This is consistent with the concept that the process of selection of cells making high affinity antibody proceeds somewhat more efficiently when there is a vigorous immune response. However, the major factors determining antibody affinity appear to be the antigen dose and the “selective pressure” of decreasing antigen concentration.