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Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses

Author

Listed:
  • Javier Rodríguez-Ubreva

    (Josep Carreras Research Institute (IJC), Badalona
    L’Hospitalet de Llobregat)

  • Anna Arutyunyan

    (Wellcome Genome Campus
    University of Cambridge)

  • Marc Jan Bonder

    (Wellcome Genome Campus
    Genome Biology Unit
    German Cancer Research Center (DKFZ))

  • Lucía Del Pino-Molina

    (Center for Biomedical Network Research on Rare Diseases (CIBERER U767))

  • Stephen J. Clark

    (Babraham Institute)

  • Carlos de la Calle-Fabregat

    (Josep Carreras Research Institute (IJC), Badalona
    L’Hospitalet de Llobregat)

  • Luz Garcia-Alonso

    (Wellcome Genome Campus)

  • Louis-François Handfield

    (Wellcome Genome Campus)

  • Laura Ciudad

    (Josep Carreras Research Institute (IJC), Badalona
    L’Hospitalet de Llobregat)

  • Eduardo Andrés-León

    (Consejo Superior de Investigaciones Científicas (IPBLN-CSIC))

  • Felix Krueger

    (Babraham Institute)

  • Francesc Català-Moll

    (Josep Carreras Research Institute (IJC), Badalona
    L’Hospitalet de Llobregat)

  • Virginia C. Rodríguez-Cortez

    (L’Hospitalet de Llobregat)

  • Krzysztof Polanski

    (Wellcome Genome Campus)

  • Lira Mamanova

    (Wellcome Genome Campus)

  • Stijn van Dongen

    (Wellcome Genome Campus)

  • Vladimir Yu. Kiselev

    (Wellcome Genome Campus)

  • María T. Martínez-Saavedra

    (Hospital Universitario de Gran Canaria Dr Negrín)

  • Holger Heyn

    (Barcelona Institute of Science and Technology (BIST)
    Universitat Pompeu Fabra (UPF))

  • Javier Martín

    (Consejo Superior de Investigaciones Científicas (IPBLN-CSIC))

  • Klaus Warnatz

    (University of Freiburg
    University of Freiburg)

  • Eduardo López-Granados

    (Center for Biomedical Network Research on Rare Diseases (CIBERER U767))

  • Carlos Rodríguez-Gallego

    (Hospital Universitario de Gran Canaria Dr Negrín
    University Fernando Pessoa)

  • Oliver Stegle

    (Wellcome Genome Campus
    Genome Biology Unit
    German Cancer Research Center (DKFZ)
    Wellcome Trust Genome Campus)

  • Gavin Kelsey

    (University of Cambridge
    Babraham Institute)

  • Roser Vento-Tormo

    (Wellcome Genome Campus
    University of Cambridge)

  • Esteban Ballestar

    (Josep Carreras Research Institute (IJC), Badalona
    L’Hospitalet de Llobregat
    East China Normal University (ECNU))

Abstract

Common variable immunodeficiency (CVID), the most prevalent symptomatic primary immunodeficiency, displays impaired terminal B-cell differentiation and defective antibody responses. Incomplete genetic penetrance and ample phenotypic expressivity in CVID suggest the participation of additional pathogenic mechanisms. Monozygotic (MZ) twins discordant for CVID are uniquely valuable for studying the contribution of epigenetics to the disease. Here, we generate a single-cell epigenomics and transcriptomics census of naïve-to-memory B cell differentiation in a CVID-discordant MZ twin pair. Our analysis identifies DNA methylation, chromatin accessibility and transcriptional defects in memory B-cells mirroring defective cell-cell communication upon activation. These findings are validated in a cohort of CVID patients and healthy donors. Our findings provide a comprehensive multi-omics map of alterations in naïve-to-memory B-cell transition in CVID and indicate links between the epigenome and immune cell cross-talk. Our resource, publicly available at the Human Cell Atlas, gives insight into future diagnosis and treatments of CVID patients.

Suggested Citation

  • Javier Rodríguez-Ubreva & Anna Arutyunyan & Marc Jan Bonder & Lucía Del Pino-Molina & Stephen J. Clark & Carlos de la Calle-Fabregat & Luz Garcia-Alonso & Louis-François Handfield & Laura Ciudad & Edu, 2022. "Single-cell Atlas of common variable immunodeficiency shows germinal center-associated epigenetic dysregulation in B-cell responses," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29450-x
    DOI: 10.1038/s41467-022-29450-x
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    References listed on IDEAS

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