Abstract

The VH replacement process is a RAG-mediated secondary recombination in which the variable region of a rearranged VHDJH is replaced by a different germline VH gene. In almost all human and mouse VH genes, two sequence features appear to be crucial for VH replacement. First, an embedded heptamer, which is located near the 3′ end of the rearranged VH gene, serves as a cryptic recombination signal sequence (3′cRSS) for the VH replacement process. Second, a short stretch of nucleotides located downstream of the 3′cRSS serve as a footprint of the original VH region, frequently encoding charged amino acids. In this review, we show that both of these two features are conserved in the VH genes of all jawed vertebrates, which suggests that the VH replacement process may be a conserved mechanism.

Highlights

  • In vertebrates, the largely diversified repertoire in the variable domain of immunoglobulins is initially generated through V(D)J recombination in developing B lymphocytes

  • The V(D)J recombination process is a site-specific recombination that depends on the recognition, binding, and cleavage of recombination signal sequences (RSSs) by the enzymes encoded by the recombination-activating genes 1 and 2 (RAG-1 and RAG-2)

  • Because the genomic organization of the VH genes in cartilaginous fishes and birds does not provide an advantageous condition for VH replacement (McCormack et al, 1991; Dooley and Flajnik, 2006), we will present a detailed analysis of the VH genes in the other four classes of jawed vertebrates, including six mammals, two reptiles, one amphibian, and three teleosts, to determine whether these two features have been conserved throughout the evolution of jawed vertebrates

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Summary

Introduction

The largely diversified repertoire in the variable domain of immunoglobulins is initially generated through V(D)J recombination in developing B lymphocytes. Because the genomic organization of the VH genes in cartilaginous fishes and birds does not provide an advantageous condition for VH replacement (McCormack et al, 1991; Dooley and Flajnik, 2006), we will present a detailed analysis of the VH genes in the other four classes of jawed vertebrates, including six mammals (mouse, Norway rat, guinea pig, rabbit, African elephant, and gray short-tailed opossum), two reptiles (painted turtle and anole lizard), one amphibian (western clawed frog), and three teleosts (zebrafish, Atlantic salmon, and channel catfish), to determine whether these two features have been conserved throughout the evolution of jawed vertebrates.

Results
Conclusion

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