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RIF1 integrates DNA repair and transcriptional requirements during the establishment of humoral immune responses

Author

Listed:
  • Eleni Kabrani

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Ali Rahjouei

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Charité-Universitätsmedizin Berlin)

  • Maria Berruezo-Llacuna

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Humboldt-Universität zu Berlin)

  • Svenja Ebeling

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Freie Universität Berlin)

  • Tannishtha Saha

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Freie Universität Berlin)

  • Robert Altwasser

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Charité-Universitätsmedizin Berlin)

  • Veronica Delgado-Benito

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association)

  • Rushad Pavri

    (King’s College London)

  • Michela Virgilio

    (Max Delbrück Center for Molecular Medicine in the Helmholtz Association
    Charité-Universitätsmedizin Berlin)

Abstract

The establishment of protective immune responses relies on the ability of terminally differentiated B cells to secrete a broad variety of antigen-specific antibodies with different effector functions. RIF1 is a multifunctional protein that promotes antibody isotype diversification via its DNA end protection activity during class switch recombination. In this study, we showed that RIF1 ablation resulted in increased plasmablast formation ex vivo and enhanced terminal differentiation into plasma cells upon immunization. Mechanistically, this phenotype is independent from RIF1’s role in DNA repair and class switch recombination, and reflects its ability to modulate the transcriptional status of a subset of BLIMP1 target genes. Therefore, here we show that, in addition to promoting antibody diversification, RIF1 fine-tunes the kinetics of late B cell differentiation, thus providing an additional layer of control in the establishment of humoral immunity.

Suggested Citation

  • Eleni Kabrani & Ali Rahjouei & Maria Berruezo-Llacuna & Svenja Ebeling & Tannishtha Saha & Robert Altwasser & Veronica Delgado-Benito & Rushad Pavri & Michela Virgilio, 2025. "RIF1 integrates DNA repair and transcriptional requirements during the establishment of humoral immune responses," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56166-5
    DOI: 10.1038/s41467-025-56166-5
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