CHARACTERIZATION OF A RABBIT GERM-LINE V-H GENE THAT IS A CANDIDATE DONOR FOR V-H GENE CONVERSION IN MUTANT ALICIA RABBITS

Normal rabbits preferentially rearrange the 3'-most V-H gene, V(H)1, t o encode Igs with V(H)a allotypes, which constitute the majority of ra bbit serum Igs. A gene conversion-like mechanism is employed to divers ify the primary Ab repertoire. In mutant Alicia rabbits that derived f rom a rabbit with V(H)a2 allotype, the V(H)1 gene was deleted. Our pre vious studies showed that the first functional gene (V(H)4) or V(H)1-l ike genes were rearranged in 2- to 8-wk-old homozygous Alicia. The V(H )1a2-like sequences that were found in splenic mRNA from 6-wk and olde r Alicia rabbits still had some residues that were typical of V(H)4. T he appearances of sequences resembling that of V(H)1a2 may have been c aused by gene conversions that altered the sequences of the rearranged V-H or there may have been rearrangement of upstream V(H)1a2-like gen es later in development. To investigate this further, we constructed a cosmid library and isolated a V(H)1a2-like gene, V(H)12-1-6, with a s equence almost identical to V(H)1a2. This gene had a deleted base in t he heptamer of its recombination signal sequence. However, even if thi s defect diminished or eliminated its ability to rearrange, the a2-lik e gene could have acted as a donor for gene-conversion-like alteration of rearranged V-H genes. Sequence comparisons suggested that this gen e or a gene like it could have acted as a donor for gene conversion in mutant Alicia and in normal rabbits.