A single VH family and long CDR3s are the targets for hypermutation in bovine immunoglobulin heavy chains.

Bovine immunoglobulins are made from genes belonging to a small family of closely related VH genes. In this respect cattle resemble all species of domesticated mammals, which also use one VH family. The family, named BoVH1, is homologous to the mouse Q52 family, and there are no more than 20 genes of this family in the bovine genome. Another feature of bovine heavy chains is the use of long CDR3s, which have an average of 21 codons. It seems that there are several families of long, closely related D genes rich in glycine and tyrosine responsible for this length. Sequences described as targets for mutations in other species can be found in CDR1, CDR2, and the putative D genes. The mutation mechanism starts at some point between late fetal stage and birth and seems to be antigen independent. Diversity seems to be generated by hypermutation, although other mechanisms cannot be discounted at this time. Contrary to humans and mice, which have several VH gene families comprising more than 100 genes, cattle use only a few genes and long CDR3s followed by somatic mutation to generate the necessary diversity to recognize the universe of antigens they will encounter during their life.