POLYMORPHISM OF THE FUNCTIONAL IMMUNOGLOBULIN VARIABLE REGION GENES IN THE CHICKEN BY EXCHANGE OF SEQUENCE WITH DONOR PSEUDOGENES

We have isolated a number of new allelic variants of the unique functi onal genes encoding chicken immunoglobulin heavy and light chain varia ble regions (V(H)1 and V(L)1, respectively). The distribution and natu re of nucleotide variation among these and previously identified V(H)1 and V(L)1 alleles demonstrates that random point mutations are likely not the predominant cause of allelic variation at these loci. Compari son of the variant nucleotides with sequences from the pseudo-VH and p seudo-V(L) gene families, which lie 5' to V(H)1 and V(L)1, respectivel y, suggests that the great majority of allelic variants can be account ed for by segmental transfer of sequence from donor pseudogenes into t he germ-line V(H)1 and V(L)1 genes. These results demonstrate that the chicken V(H)1 and V(L)1 genes are susceptible to sequence replacement at the germ-line level as well as somatically during antibody diversi fication. The limited repertoire of B cell specificities produced by g ene rearrangement in the chicken has led to speculation that these spe cificities may play a critical role in the progression of chicken B ce ll development. The results presented here do not support this hypothe sis since many of the allelic variant nucleotides described here encod e non-conservative amino acid substitutions within the antigen-binding sites of the Ig molecule.