Yuko Ohta* and Martin Flajnik
Proc Natl Acad Sci U S A. 2006 July 11; 103(28): 10723-10728. Published online 2006 July 3. doi: 10.1073/pnas.0601407103.
Copyright © 2006 by The National Academy of Sciences of the USA Department of Microbiology and Immunology, University of Maryland, 655 West Baltimore Street, Baltimore, MD 21201
*To whom correspondence should be addressed.
Edited by Gustav J. Nossal, University of Melbourne, Victoria, Australia, and approved June 1, 2006
Author contributions: Y.O. and M.F. designed research; Y.O. performed research; M.F. contributed new reagents/analytic tools; Y.O. analyzed data; and Y.O. and M.F. wrote the paper.
Received February 19, 2006.
IgD has remained a mysterious Ig class and a bane to immunology students since its discovery >40 years ago. Its spotty occurrence in mammals and birds and the discovery of an isotype with similarities to IgD in bony fish are perplexing.
We have identified IgD heavy (H) chain (d) from the amphibian Xenopus tropicalis during examination of the IgH locus. The Xenopus d gene is in the same position, immediately 3' of the IgM gene, as in mammals, and it is expressed only in the spleen at low levels, primarily as a transmembrane receptor by surface IgM+ cells.
Our data suggest that frog IgD is expressed on mature B cells, like in mouse/human. Unexpectedly, Xenopus IgD is orthologous to IgW, an Ig isotype found only in cartilaginous fish and lungfish, demonstrating that IgD/W, like IgM, was present in the ancestor of all living jawed vertebrates.
In striking contrast to IgM, IgD/W is evolutionarily labile, showing many duplications/deletions of domains, the presence of multiple splice forms, existence as predominantly a secretory or transmembrane form, or loss of the entire gene in a species-specific manner.
Our study suggests that IgD/W has played varied roles in different vertebrate taxa since the inception of the adaptive immune system, and it may have been preserved as a flexible locus over evolutionary time to complement steadfast IgM.