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High frequency of shared clonotypes in human B cell receptor repertoires

Author

Listed:
  • Cinque Soto

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

  • Robin G. Bombardi

    (Vanderbilt University Medical Center)

  • Andre Branchizio

    (Vanderbilt University Medical Center)

  • Nurgun Kose

    (Vanderbilt University Medical Center)

  • Pranathi Matta

    (Vanderbilt University Medical Center)

  • Alexander M. Sevy

    (Vanderbilt University)

  • Robert S. Sinkovits

    (University of California, San Diego)

  • Pavlo Gilchuk

    (Vanderbilt University Medical Center)

  • Jessica A. Finn

    (Vanderbilt University)

  • James E. Crowe

    (Vanderbilt University Medical Center
    Vanderbilt University Medical Center
    Vanderbilt University Medical Center)

Abstract

The human genome contains approximately 20 thousand protein-coding genes1, but the size of the collection of antigen receptors of the adaptive immune system that is generated by the recombination of gene segments with non-templated junctional additions (on B cells) is unknown—although it is certainly orders of magnitude larger. It has not been established whether individuals possess unique (or private) repertoires or substantial components of shared (or public) repertoires. Here we sequence recombined and expressed B cell receptor genes in several individuals to determine the size of their B cell receptor repertoires, and the extent to which these are shared between individuals. Our experiments revealed that the circulating repertoire of each individual contained between 9 and 17 million B cell clonotypes. The three individuals that we studied shared many clonotypes, including between 1 and 6% of B cell heavy-chain clonotypes shared between two subjects (0.3% of clonotypes shared by all three) and 20 to 34% of λ or κ light chains shared between two subjects (16 or 22% of λ or κ light chains, respectively, were shared by all three). Some of the B cell clonotypes had thousands of clones, or somatic variants, within the clonotype lineage. Although some of these shared lineages might be driven by exposure to common antigens, previous exposure to foreign antigens was not the only force that shaped the shared repertoires, as we also identified shared clonotypes in umbilical cord blood samples and all adult repertoires. The unexpectedly high prevalence of shared clonotypes in B cell repertoires, and identification of the sequences of these shared clonotypes, should enable better understanding of the role of B cell immune repertoires in health and disease.

Suggested Citation

  • Cinque Soto & Robin G. Bombardi & Andre Branchizio & Nurgun Kose & Pranathi Matta & Alexander M. Sevy & Robert S. Sinkovits & Pavlo Gilchuk & Jessica A. Finn & James E. Crowe, 2019. "High frequency of shared clonotypes in human B cell receptor repertoires," Nature, Nature, vol. 566(7744), pages 398-402, February.
  • Handle: RePEc:nat:nature:v:566:y:2019:i:7744:d:10.1038_s41586-019-0934-8
    DOI: 10.1038/s41586-019-0934-8
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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. Nina G. Bozhanova & Andrew I. Flyak & Benjamin P. Brown & Stormy E. Ruiz & Jordan Salas & Semi Rho & Robin G. Bombardi & Luke Myers & Cinque Soto & Justin R. Bailey & James E. Crowe & Pamela J. Bjorkm, 2022. "Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. 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.
    4. 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.
    5. 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.
    6. Noemia S. Lima & Maryam Musayev & Timothy S. Johnston & Danielle A. Wagner & Amy R. Henry & Lingshu Wang & Eun Sung Yang & Yi Zhang & Kevina Birungi & Walker P. Black & Sijy O’Dell & Stephen D. Schmid, 2022. "Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. Chaim A. Schramm & Damee Moon & Lowrey Peyton & Noemia S. Lima & Christian Wake & Kristin L. Boswell & Amy R. Henry & Farida Laboune & David Ambrozak & Samuel W. Darko & I-Ting Teng & Kathryn E. Fould, 2023. "Interaction dynamics between innate and adaptive immune cells responding to SARS-CoV-2 vaccination in non-human primates," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. Garrett Dunlap & Aaron Wagner & Nida Meednu & Ruoqiao Wang & Fan Zhang & Jabea Cyril Ekabe & Anna Helena Jonsson & Kevin Wei & Saori Sakaue & Aparna Nathan & Vivian P. Bykerk & Laura T. Donlin & Susan, 2024. "Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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