Insights into the function of IgD

IgD, previously thought to be a recent addition to the immunoglobulin classes, has long been considered an enigmatic molecule. For example, it was debated if IgD had a specific function other than as an antigen receptor co-expressed with IgM on naive B cells and if it had an important role in mammalian immunity. However, during the past decade extensive sequencing of vertebrate genomes has shown that IgD homologs are present in all vertebrate taxa, except for birds. Moreover, recent functional studies indicate that IgD likely performs a unique role in vertebrate immune responses. The goal of this review is to summarize the IgD gene organization and structural data, which demonstrate that IgD has an ancient origin, and discuss the findings in catfish and humans that provide insight into the possible function of this elusive immunoglobulin isotype.