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Molecular bases of genetic diversity and evolution of the immunoglobulin heavy chain variable region (IGHV) gene locus in leporids

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Abstract

The rabbit has long been a model for studies of the immune system. Work using rabbits contributed both to the battle against infectious diseases such as rabies and syphilis, and to our knowledge, of antibodies' structure, function, and regulated expression. With the description of rabbit Ig allotypes, the discovery of different gene segments encoding immunoglobulins became possible. This challenged the “one gene–one protein” dogma. The observation that rabbit allotypic specificities of the variable regions were present on IgM and IgG molecules also led to the hypothesis of Ig class switching. Rabbit allotypes contributed to the documentation of phenomena such as allelic exclusion and imbalance in production of allelic gene products. During the last 30 years, the rabbit Ig allotypes revealed a number of unique features, setting them apart from mice, humans, and other mammals. Here, we review the most relevant findings concerning the rabbit IGHV. Among these are the preferential usage of one VH gene in VDJ rearrangements, the existence of trans-species polymorphism in the IGHV locus revealed by serology and confirmed by sequencing IGHV genes in Lepus, the unusually large genetic distances between allelic lineages and the fact that the antibody repertoire is diversified in this species only after birth. The whole genome sequence of a rabbit, plus re-sequencing of additional strains and related genera, will allow further evolutionary investigations of antibody variation. Continued research will help define the roles that genetic, allelic, and population diversity at antibody loci may play in host-parasite interactions.

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Acknowledgments

This work was supported by grants of Foundation for Science and Technology—Portugal to A.P. and P.J.E. (SFRH/BD/71252/2010 and SFRH/BPD/27021/2006), respectively, and the intramural program of the NIAID, NIH (R.G.M.).

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Authors and Affiliations

  1. Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, Campus Agrário de Vairão, 4485–661, Vairão, Portugal

    Ana Pinheiro, Paulo C. Alves, Wessel van der Loo & Pedro J. Esteves

  2. Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, 4169–007, Porto, Portugal

    Ana Pinheiro & Paulo C. Alves

  3. Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, 60153, USA

    Dennis Lanning & Katherine L. Knight

  4. Laboratory of Immunology, NIAID, National Institutes of Health, Bethesda, MD, 20892, USA

    Rose G. Mage

  5. Centro de Investigação em Tecnologias da Saúde, IPSN, CESPU, 4585–116, Gandra, Portugal

    Pedro J. Esteves

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  2. Dennis Lanning
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  3. Paulo C. Alves
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  7. Pedro J. Esteves
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Correspondence to Pedro J. Esteves.

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Pinheiro, A., Lanning, D., Alves, P.C. et al. Molecular bases of genetic diversity and evolution of the immunoglobulin heavy chain variable region (IGHV) gene locus in leporids. Immunogenetics 63, 397–408 (2011). https://doi.org/10.1007/s00251-011-0533-9

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  • DOI: https://doi.org/10.1007/s00251-011-0533-9

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