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Commonality despite exceptional diversity in the baseline human antibody repertoire

Author

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  • Bryan Briney

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute
    IAVI Neutralizing Antibody Center, The Scripps Research Institute)

  • Anne Inderbitzin

    (The Scripps Research Institute
    University Hospital Zurich, University of Zurich)

  • Collin Joyce

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute
    IAVI Neutralizing Antibody Center, The Scripps Research Institute)

  • Dennis R. Burton

    (The Scripps Research Institute
    The Scripps Research Institute
    IAVI Neutralizing Antibody Center, The Scripps Research Institute
    Human Vaccines Project)

Abstract

In principle, humans can produce an antibody response to any non-self-antigen molecule in the appropriate context. This flexibility is achieved by the presence of a large repertoire of naive antibodies, the diversity of which is expanded by somatic hypermutation following antigen exposure1. The diversity of the naive antibody repertoire in humans is estimated to be at least 1012 unique antibodies2. Because the number of peripheral blood B cells in a healthy adult human is on the order of 5 × 109, the circulating B cell population samples only a small fraction of this diversity. Full-scale analyses of human antibody repertoires have been prohibitively difficult, primarily owing to their massive size. The amount of information encoded by all of the rearranged antibody and T cell receptor genes in one person—the ‘genome’ of the adaptive immune system—exceeds the size of the human genome by more than four orders of magnitude. Furthermore, because much of the B lymphocyte population is localized in organs or tissues that cannot be comprehensively sampled from living subjects, human repertoire studies have focused on circulating B cells3. Here we examine the circulating B cell populations of ten human subjects and present what is, to our knowledge, the largest single collection of adaptive immune receptor sequences described to date, comprising almost 3 billion antibody heavy-chain sequences. This dataset enables genetic study of the baseline human antibody repertoire at an unprecedented depth and granularity, which reveals largely unique repertoires for each individual studied, a subpopulation of universally shared antibody clonotypes, and an exceptional overall diversity of the antibody repertoire.

Suggested Citation

  • Bryan Briney & Anne Inderbitzin & Collin Joyce & Dennis R. Burton, 2019. "Commonality despite exceptional diversity in the baseline human antibody repertoire," Nature, Nature, vol. 566(7744), pages 393-397, February.
  • Handle: RePEc:nat:nature:v:566:y:2019:i:7744:d:10.1038_s41586-019-0879-y
    DOI: 10.1038/s41586-019-0879-y
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    Citations

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    Cited by:

    1. Aleksandr Kovaltsuk & Matthew I J Raybould & Wing Ki Wong & Claire Marks & Sebastian Kelm & James Snowden & Johannes Trück & Charlotte M Deane, 2020. "Structural diversity of B-cell receptor repertoires along the B-cell differentiation axis in humans and mice," PLOS Computational Biology, Public Library of Science, vol. 16(2), pages 1-20, February.
    2. Mathieu Claireaux & Tom G. Caniels & Marlon Gast & Julianna Han & Denise Guerra & Gius Kerster & Barbera D. C. Schaik & Aldo Jongejan & Angela I. Schriek & Marloes Grobben & Philip J. M. Brouwer & Kar, 2022. "A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Oscar L. Rodriguez & Yana Safonova & Catherine A. Silver & Kaitlyn Shields & William S. Gibson & Justin T. Kos & David Tieri & Hanzhong Ke & Katherine J. L. Jackson & Scott D. Boyd & Melissa L. Smith , 2023. "Genetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Yubin Liu & Ziyi Wang & Xinyu Zhuang & Shengnan Zhang & Zhicheng Chen & Yan Zou & Jie Sheng & Tianpeng Li & Wanbo Tai & Jinfang Yu & Yanqun Wang & Zhaoyong Zhang & Yunfeng Chen & Liangqin Tong & Xi Yu, 2023. "Inactivated vaccine-elicited potent antibodies can broadly neutralize SARS-CoV-2 circulating variants," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    5. Christoph Kreer & Cosimo Lupo & Meryem S. Ercanoglu & Lutz Gieselmann & Natanael Spisak & Jan Grossbach & Maike Schlotz & Philipp Schommers & Henning Gruell & Leona Dold & Andreas Beyer & Armita Nourm, 2023. "Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Nima Nouri & Steven H Kleinstein, 2020. "Somatic hypermutation analysis for improved identification of B cell clonal families from next-generation sequencing data," PLOS Computational Biology, Public Library of Science, vol. 16(6), pages 1-22, June.
    7. Eduardo Gomez-Bañuelos & Yikai Yu & Jessica Li & Kevin S. Cashman & Merlin Paz & Maria Isabel Trejo-Zambrano & Regina Bugrovsky & Youliang Wang & Asiya Seema Chida & Cheryl A. Sherman-Baust & Dylan P., 2023. "Affinity maturation generates pathogenic antibodies with dual reactivity to DNase1L3 and dsDNA in systemic lupus erythematosus," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    8. Chengzi I. Kaku & Tyler N. Starr & Panpan Zhou & Haley L. Dugan & Paul Khalifé & Ge Song & Elizabeth R. Champney & Daniel W. Mielcarz & James C. Geoghegan & Dennis R. Burton & Raiees Andrabi & Jesse D, 2023. "Evolution of antibody immunity following Omicron BA.1 breakthrough infection," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    9. Joan Capella-Pujol & Marlon Gast & Laura Radić & Ian Zon & Ana Chumbe & Sylvie Koekkoek & Wouter Olijhoek & Janke Schinkel & Marit J. Gils & Rogier W. Sanders & Kwinten Sliepen, 2023. "Signatures of VH1-69-derived hepatitis C virus neutralizing antibody precursors defined by binding to envelope glycoproteins," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    10. Yi-Chun Hsiao & Heidi Ackerly Wallweber & Robert G. Alberstein & Zhonghua Lin & Changchun Du & Ainhoa Etxeberria & Theint Aung & Yonglei Shang & Dhaya Seshasayee & Franziska Seeger & Andrew M. Watkins, 2024. "Rapid affinity optimization of an anti-TREM2 clinical lead antibody by cross-lineage immune repertoire mining," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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