Immunological Maturation

Immunological maturation, the gradual increase in affinity for antigen of serum antibody with time after immunization, has been postulated to result from a competition among precursors of antibody-forming cells for available antigen (1, 2). Thus, as the antigen concentration in the cellular environment falls, only those cells with antigen-binding receptors of sufficiently high avidity to capture antigen will continue to be stimulated, proliferate, and mature into antibody-secreting cells. Furthermore, this thesis requires that the binding characteristics of the receptor on the precursor cell are identical, or very similar, to those of the antibody produced by the descendents. Results from our previous studies have supported this view (3, 4). In them, we have shown that immune maturation results from the relative persistence of high-affinity antibody-producing cells later after immunization while the number of cells secreting lower affinity antibody falls rapidly after the early days of the immune response. This conclusion was based on an analysis of individual anti-2,4-dinitrophenyl (DNP) anti-body-secreting cells in guinea pigs immunized with 50 ttg of dinitrophenyl guinea pig albumin (DNP-GPA). By dividing the antibody-secreting cell population at each time point into avidity groups (see below), it was possible to follow independently the changes in frequency of cells producing antibody of different affinities. It was found that among the population of antibody-secreting cells which appeared in draining lymph nodes shortly after immunization were relatively large numbers of cells secreting high-affinity as well as cells secreting intermediate-and low-at~nity antibody. The exponential increase in the number of antibody-secreting cells which occurred during the first few days of the response was an increase in frequency of cells in each avidity group. After 12 days, however, the relative frequencies of antibody-secreting cells in the various avidity groups changed markedly. The number of cells in the lower avidity groups began to fall in frequency while the number of cells in the higher avidity groups was preserved. By day 30, only high-avidity producers remained. These changes are most easily explained in terms of the original hypothesis of maturation based on competition for antigen. I t would be expected that the changes in relative frequencies among cells producing antibody of various affinities would be preceded by similar changes in the proliferation rate of precursors. We present evidence here that this is so. Adult strain 13 guinea pigs were immunized by injection, into the footpads, of 50 ttg of DNP23-GPA emulsified in complete Freund's adjuvant (CFA). …