Limited number of immunoglobulin V H regions expressed in the mutant rabbit “Alicia”

A unique feature of rabbit Ig is the presence of V H region allotypic specificities. In normal rabbits, more than 80% of circulating immunoglobulin molecules bear theV H a allotypic specificities, a1, a2 or a3; the remaining 10% to 20% of immunoglobulin molecules lack V H a allotypic specificities and are designated V H a − . A mutant rabbit designated Alicia, in contrast, has predominantly serumimmunoglobulin molecules that lack the V H a allotypic specificities (Kelus and Weiss, Proc. Natl. Acad. Sci. USA 1986. 83: 4883). To study the nature and molecular complexity of V H a − molecules, we cloned and determined the nucleotide sequence of seven cDNA prepared from splenic RNA of an Alicia rabbit. Six ofthe clones appeared to encode V H a − molecules; the framework regions encoded by these clones were remarkably similar to each other, each having an unusual insertion of four amino acids at position 10. This insertion of four amino acids has beenseen in only 2 of 54 sequenced rabbit V H genes. The similarity of the sequences of the six V H a − clones to each other and their dissimilarity to most other V H genes leads us to suggest that the V H a − molecules in Alicia rabbits are derived predominantly from one or a small number of very similar V H genes. Such preferential utilization of a small number of V H genes may explain the allelic inheritance of V H allotypes.