Inheritance of Antibody Specificity

Our data suggest that fine specificity of antihapten antibodies is a useful Mendelian marker of variable (V) genes. We found that some mouse strains (e.g., C57/BL6) consistently produced heteroclitic anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibodies (relative affinity for related (4-hydroxy-5-iodo-3-nitrophenyl)acetyl and (4-hydroxy-3.5-dinitrophenyl)acetyl was always >2) while other strains (e.g., CBA) produced "conventional" anti-NP antibodies (relative affinities were consistently <1). 48 (CBA x C57BL/6)F(1) mice were studied and most of them had heteroclitic anti-NP antibodies. They were backcrossed to the recessive CBA parent, and 87 backcross animals were similarly tested. Those heterozygous for the C57BL/6 heavy (H)-chain allotype were similar to the C57BL/6 and the F(1) mice while mice homozygous for the CBA allotype were indistinguishable from the CBA. Such monogenic inheritance was observed only in the primary response. Predominance of allotype-linked genes in the control of the fine specificity characteristics was confirmed by immunizing selected homozygous mouse strains. These mice contained various mixtures of genes from C57BL, BALB/c, and other strains. Specificity of their anti-NP was exclusively determined by genes linked to the H-chain allotype, no influence could be attributed to other genes including the H-2-linked genes.