Multiple IgH Isotypes Including IgD, Subclasses of IgM, and IgY Are Expressed in the Common Ancestors of Modern Birds

Abstract

Although evolutionarily just as ancient as IgM, it has been thought for many years that IgD is not present in birds. Based on the recently sequenced genomes of 48 bird species as well as high-throughput transcriptome sequencing of immune-related tissues, we demonstrate in this work that the ostrich (Struthio camelus) possesses a functional δ gene that encodes a membrane-bound IgD H chain with seven CH domains. Furthermore, δ sequences were clearly identified in many other bird species, demonstrating that the δ gene is widely distributed among birds and is only absent in certain bird species. We also show that the ostrich possesses two μ genes (μ1, μ2) and two υ genes (υ1, υ2), in addition to the δ and α genes. Phylogenetic analyses suggest that subclass diversification of both the μ and υ genes occurred during the early stages of bird evolution, after their divergence from nonavian reptiles. Although the positions of the two υ genes are unknown, physical mapping showed that the remaining genes are organized in the order μ1-δ-α-μ2, with the α gene being inverted relative to the others. Together with previous studies, our data suggest that birds and nonavian reptile species most likely shared a common ancestral IgH gene locus containing a δ gene and an inverted α gene. The δ gene was then evolutionarily lost in selected birds, whereas the α gene lost in selected nonavian reptiles. The data obtained in this study provide significant insights into the understanding of IgH gene evolution in tetrapods.

Three IgH isotypes, IgM, IgA and IgY are expressed in Gentoo penguin and zebra finch

“…To date, it has been reported that there are three functional μ genes in the crocodilian IgH locus and two in the ostrich and emu, and at least four Squamata species have more than one μ gene [4, 35, 38]. The isotypes mentioned above originated from duplications of the exons that encode for the C μ located at the 5’ end.…”

Molecular characterization and expression analysis of three subclasses of IgT in rainbow trout (Oncorhynchus mykiss)

“…Human and mouse also possess certain subclasses of IgG (French and Harrison, 1984) and IgA (Kett et al, 1986), which enable more subtle immune responses. Among those Igs, IgM and IgD are evolutionarily conserved and are thought to be the primordial Ig isotypes (Edholm et al, 2011; Han et al, 2016). However in teleosts, IgM (Bradshaw et al, 1971; Hordvik et al, 2013), IgD (Edholm et al, 2010; Ramirez-Gomez et al, 2012; Wilson et al, 1997) and IgT or IgZ (H chain: τ or ζ) (Hansen et al, 2005; Hu et al, 2010) have been identified in various fish species.…”

IgD attenuates the IgM-induced anergy response in transitional and mature B cells

“…22), which facilitates alternative mRNA splicing of the heavy chain variable (VDJ H ) exon to either IgM or IgD heavy chain constant (C)-region exons. This arrangement is evolutionarily preserved in most species of fish, amphibians, reptiles, birds and mammals1723, yet mice lacking IgD have normal B cell development and only slightly delayed antibody responses2425. Likewise, comparison of mice that express only IgM or only IgD reveals no discernable difference in the capacity of these alternative receptors to promote B cell development, tolerance, activation or antibody secretion in vivo 2627.…”