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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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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DOI: https://doi.org/10.1038/gene.2012.20
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