Shark IgW C Region Diversification through RNA Processing and Isotype Switching

摘要: Sharks and skates represent the earliest vertebrates with an adaptive immune system based on lymphocyte Ag receptors generated by V(D)J recombination. Shark B cells express two classical Igs, IgM IgW, encoded early, alternative gene organization consisting of numerous autonomous miniloci, where individual cluster carries a few rearranging segments one C region, μ or ω. We have characterized eight distinct Ig miniloci encoding nurse shark ω H chain. Each consists VH, D, JH six to domain exons. Two interspersed secretory exons, in addition 3'-most exon tailpiece, provide ability generate at least secreted isoforms that differ as polypeptide length combination. All clusters appear be functional, judged capability for rearrangement absence defects deduced amino acid sequence. previously showed IgW VDJ can perform isotype switching regions; this study, we found also occurs between clusters. Thus, region diversification any take place DNA level other regions, well RNA processing different isoforms. The wide array pathogens recognized Abs requires disposal pathways, our findings demonstrate complex unique pathways effector function diversity evolved independently cartilaginous fishes.