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Current Trends in Immunology   Volumes    Volume 4 
Immunoglobulin genes and their diversification in vertebrates
Surinder S. Saini, Azad Kaushik
Pages: 161 - 176
Number of pages: 16
Current Trends in Immunology
Volume 4 

Copyright © 2002 Research Trends. All rights reserved


Studies in phylogenetically distant species demonstrate differences in the structure and organization of VH and VL genes that have evolved along several lines advancing our understanding of the construction of the immune system during evolution. Multiple VH gene families of elasmobranchs and ratfish are organized as V- D1-D2J or VD-J or VDJ units that restrict the combanitorial diversity among these species. The VH genes in nurse shark undergo rearrangement and somatic hypermutations. In addition to IgM, other isotypes found among elasmobranchs include IgX (skate), NAR (nurse shark), IgNARC (cartilaginous fish) and IgW (sandbar shark). Multiple VH gene families also exist in the genome of bony fish. The VH genes of amphibians are grouped into 11 families and undergo rearrangement but generate limited antibody diversity in larvae as compared to diverse antibody repertoire of adults, probably due to the differences in the expression of TdT enzyme and functional germinal centres in the lymphoid organs. Four VH gene families and a number of JH gene segments have been identified in turtle. A single family of VH genes identified in chicken, rabbit and swine belong to evolutionarily conserved mammalian group III VH genes whereas those in horse, sheep and cattle belong to evolutionarily less conserved mammalian group I VH genes.

The Ig L chain genes of cartilaginous and bony fish cannot be classified either as κ- or λ.-L chains of higher vertebrates. However, type I and III light-chain genes of Xenopus share high nucleotide homology with mammalian κ- and λ-L chains, respectively. The clustered  organization of L chain genes in elasmobranchs and teleost fish restrict the antibody diversity. In comparison to limited number of functional germline VL genes in species like chicken, rabbit and cattle, multiple VL gene families exist at murine κ- and human κ- and λ-L chain loci.

The recombination process alone is unable to generate antibody diversity essential to normal immune function and host defence in species with restricted germline pool of variable region genes. These species thus diversify the antibody repertoire through alternate strategies such as gene conversion e.g., chicken and rabbit, non-antigen dependant somatic hypermutations e.g., sheep and generation of exceptionally long CDR3H regions e.g., cattle. Such natural mechanisms for generation of antibody diversity in vertebrates provide novel approaches to development of therapeutic antibodies and vaccines via genetic engineering.


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