The effect of antigen and mode of immunization on the allotypic distribution of enhanceable plaque-forming antibody.

Abstract

AbstractThe relation between the genotypic control and phenotypic expression of antibody formation and between gene dose and product concentration depends on and is modified by antigen‐mediated selection and by antigen‐induced cell division. This dependence was studied in terms of allotypic specificities of rabbit light chain as markers and with different antigens and. regimens of immunization. The number of enhanceable plaque‐forming cells of the same allotype was measured in the spleens of rabbits, homozygous and heterozygous at the Ab locus. A significant departure from a simple gene‐dose relationship was observed. The regular preponderance of one allotype over another (“pecking order”: A4>A6>A5>A9) was confirmed. The preponderance in A4/A5 animals was found to persist whether the allotype ratio of enhanceable plaques was tested after one, two or ten injections with SRBC, after immunization with chemically modified SRBC or with DNP‐HGG. There was no significant difference in the cross‐reactivity of A4 and AS plaque‐forming SRBC antibody. The distribution of allotype ratios of responding A4/A5 animals changed with prolonged immunization from trimodal to bimodal and finally approached unimodality. After two injections with SRBC, the incidence of individual heterozygotes, making a monoallotypic enhanceable plaque response, was greatest among animals with allotypes from the extremes of the pecking order (i.e. A4/A9).We can account for our observations and for the distribution of allotype ratios in the response to strong and to weak antigen on the basis of the following assumptions: a small number of receptor‐carrying precursors of antibody‐forming cells is involved in the response to one cr two injections with antigen; the specificity spectrum for antigens which evoke a heterogeneous response is the same for plaque‐forming antibodies of different allotypic specificity (A4 or A5); in heterozygotes, the ratio of receptors with different allotypic specificities is different from 1 and is related to the distance in the pecking order; the greater the distance, the greater the difference from 1; there is continuous recruitment from precursor cells during prolonged immunization.