Inheritance of antibody specificity. III. A new VH gene controls fine specificity of anti-p-azobenzenearsonate coupled to the carbon atom 5 of hydroxyphenylacetic acid in the mouse.

Mice of 10 inbred strains were immunized with a protein conjugate of a hapten of p-azobenzenearsonate coupled to the carbon atom 5 of hydroxphenylacetic acid (ABA-HOP), and anti-ABA-HOP titers were determined by the haptenated phage inactivation. Mean titers of C57BL/6 and BALB/c mice were significantly lower than those of A/J and CBA strains. The titers were under a polygenic control and did not correlate with allotypes in backcross mice. Fine specificity of the anti-ABA-HOP was characterized by inhibiting the haptenated phage inactivation reaction with five chemically related compounds including ABA-HOP (Fig. 1). This antibody was genetically more polymorphic than any other antibody studied. Three distinct idiotypes could be demonstrated and the number is probably greater. The idiotypes of the A/J and C57BL/6 were inherited as allotype-linked dominant Mendelian traits, the former in two and the latter in three different backcrosses. Condominance of the two alleles was shown since approximately equal amounts of the two idiotypes were produced by the population of heterozygous mice. There were many individual heterozygotes, however, in which only one parental idiotype could be detected. In other individuals of the same genotype the other parental idiotype was predominant. In many mice a mixture of the two idiotypes was indicated by doubly sigmoid inhibition curves. The causes for the variation in the expression of the two alleles in genotypically identical mice is discussed.