An almost absolute selection in favor of allotype b4 occurs in the antibody response of heterozygous b4b9 rabbits immunized with Group C streptococcal vaccine. A possible explanation for this “allelic selection” in favor of b4 is that during the antistreptococcal response the favored allotype (b4) is associated with V region binding sites yielding higher avidity anti-streptococcal antibodies. In order to test this possibility, IgG from heterozygous, hyperimmune rabbits was fractionated by avidity on a Group C immunoadsorbent column and allotypes of the various fractions were quantitatively determined. Contrary to the predicted result, when secondary immunization sera were examined the fractions of highest avidity were enriched in the nonselected allotype. Antibodies from two primary immunization sera lacked the selection for the non-b4 allotype in high avidity fractions observed for the later sera. Thus, the uneven allotype ratios observed in fractions of different avidity from secondary immunization sera can be interpreted as the result of a secondary maturation effect.
The observations of allelic selection in heterozygous rabbits were extended to rabbits with allotypes b4b5 and b4b6. Although b4 predominated in immunoglobulin from these rabbits, the allotype ratios in anti-streptococcal antibody were the same as those in total IgG before immunization.
This work was supported by Grant AI 11439 from the United States Public Health Service.