Artiodactyl IgD: The missing link

IgD has been suggested to be a recently developed Ig class, only present in rodents and primates. However, in this paper the cow, sheep, and pig Ig ⊃ genes have been identified and shown to be transcriptionally active. The deduced amino acid sequences from their cDNAs show that artiodactyl IgD H chains are structurally similar to human IgD, where the cow, sheep, and pig IgD H chain constant regions all contain three domains and a hinge region, sharing homologies of 43.6, 44, and 46.8% with their human counterpart, respectively. According to a phylogenetic analysis, the Cδ gene appears to have been duplicated from the Cμ gene ≥300 million yr ago. The ruminant μCH1 exon and its upstream region was again duplicated before the speciation of the cow and sheep, ∼20 million yr ago, inserted upstream of the δ gene hinge regions, and later modified by gene conversion. A short Sδ (switch δ) sequence resulting from the second duplication, is located immediately upstream of the bovine Cδ gene and directs regular μ-δ class switch recombination in the cow. The presence of Cδ genes in artiodactyls, possibly in most mammals, suggests that IgD may have some as yet unknown biological properties, distinct from those of IgM, conferring a survival advantage.