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B cell class switch recombination is regulated by DYRK1A through MSH6 phosphorylation

Author

Listed:
  • Liat Stoler-Barak

    (Weizmann Institute of Science)

  • Ethan Harris

    (St. Jude Children’s Research Hospital)

  • Ayelet Peres

    (Bar Ilan University)

  • Hadas Hezroni

    (Weizmann Institute of Science)

  • Mirela Kuka

    (Vita-Salute San Raffaele University and Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute)

  • Pietro Lucia

    (Vita-Salute San Raffaele University and Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute)

  • Amalie Grenov

    (Weizmann Institute of Science)

  • Neta Gurwicz

    (Weizmann Institute of Science)

  • Meital Kupervaser

    (Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science)

  • Bon Ham Yip

    (St. Jude Children’s Research Hospital)

  • Matteo Iannacone

    (Vita-Salute San Raffaele University and Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute
    IRCCS San Raffaele Scientific Institute)

  • Gur Yaari

    (Bar Ilan University)

  • John D. Crispino

    (St. Jude Children’s Research Hospital)

  • Ziv Shulman

    (Weizmann Institute of Science)

Abstract

Protection from viral infections depends on immunoglobulin isotype switching, which endows antibodies with effector functions. Here, we find that the protein kinase DYRK1A is essential for B cell-mediated protection from viral infection and effective vaccination through regulation of class switch recombination (CSR). Dyrk1a-deficient B cells are impaired in CSR activity in vivo and in vitro. Phosphoproteomic screens and kinase-activity assays identify MSH6, a DNA mismatch repair protein, as a direct substrate for DYRK1A, and deletion of a single phosphorylation site impaired CSR. After CSR and germinal center (GC) seeding, DYRK1A is required for attenuation of B cell proliferation. These findings demonstrate DYRK1A-mediated biological mechanisms of B cell immune responses that may be used for therapeutic manipulation in antibody-mediated autoimmunity.

Suggested Citation

  • Liat Stoler-Barak & Ethan Harris & Ayelet Peres & Hadas Hezroni & Mirela Kuka & Pietro Lucia & Amalie Grenov & Neta Gurwicz & Meital Kupervaser & Bon Ham Yip & Matteo Iannacone & Gur Yaari & John D. C, 2023. "B cell class switch recombination is regulated by DYRK1A through MSH6 phosphorylation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37205-5
    DOI: 10.1038/s41467-023-37205-5
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    References listed on IDEAS

    as
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