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High-throughput antibody sequencing reveals genetic evidence of global regulation of the naïve and memory repertoires that extends across individuals

Genes & Immunity volume 13, pages 469–473 (2012)Cite this article

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Abstract

Vast diversity in the antibody repertoire is a key component of the adaptive immune response. This diversity is generated centrally through the assembly of variable, diversity and joining gene segments, and peripherally by somatic hypermutation and class-switch recombination. The peripheral diversification process is thought to only occur in response to antigenic stimulus, producing antigen-selected memory B cells. Surprisingly, analyses of the variable, diversity and joining gene segments have revealed that the naïve and memory subsets are composed of similar proportions of these elements. Lacking, however, is a more detailed study, analyzing the repertoires of naïve and memory subsets at the level of the complete V(D)J recombinant. This report presents a thorough examination of V(D)J recombinants in the human peripheral blood repertoire, revealing surprisingly large repertoire differences between circulating B-cell subsets and providing genetic evidence for global control of repertoire diversity in naïve and memory circulating B-cell subsets.

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Acknowledgements

We thank all patients for participating in the study. We would like to especially thank Chris L Wright and Alvaro G Hernandez at the W. M. Keck Center for Comparative and Functional Genomics at the University of Illinois at Urbana-Champaign for performing the 454 sequencing. We are grateful to the IMGT team for its helpful collaboration and the analysis of nucleotide sequences on the IMGT/HighV-QUEST web portal.

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Authors and Affiliations

  1. Departments of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA

    B S Briney & J E Crowe Jr

  2. Departments of Chemical and Physical Biology Program, Vanderbilt University Medical Center, Nashville, TN, USA

    J R Willis

  3. Tandy School of Computer Science and Department of Mathematics, University of Tulsa, Tulsa, OK, USA

    B A McKinney

  4. Departments of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA

    J E Crowe Jr

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  1. B S Briney
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  2. J R Willis
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  3. B A McKinney
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  4. J E Crowe Jr
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Correspondence to J E Crowe Jr.

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Supplementary Information accompanies the paper on Genes and Immunity website

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Briney, B., Willis, J., McKinney, B. et al. High-throughput antibody sequencing reveals genetic evidence of global regulation of the naïve and memory repertoires that extends across individuals. Genes Immun 13, 469–473 (2012). https://doi.org/10.1038/gene.2012.20

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