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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
16 03 2023
Historique:
received: 21 06 2022
accepted: 06 03 2023
entrez: 17 3 2023
pubmed: 18 3 2023
medline: 21 3 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 36927854
doi: 10.1038/s41467-023-37205-5
pii: 10.1038/s41467-023-37205-5
pmc: PMC10020581
doi:

Substances chimiques

DNA-Binding Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1462

Informations de copyright

© 2023. The Author(s).

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Auteurs

Liat Stoler-Barak (L)

Department of Systems Immunology, Weizmann Institute of Science, Rehovot, 7610001, Israel.

Ethan Harris (E)

Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.

Ayelet Peres (A)

Faculty of Engineering, Bar Ilan University, Ramat Gan, 52900, Israel.

Hadas Hezroni (H)

Department of Systems Immunology, Weizmann Institute of Science, Rehovot, 7610001, Israel.

Mirela Kuka (M)

Vita-Salute San Raffaele University and Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Pietro Di Lucia (P)

Vita-Salute San Raffaele University and Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Amalie Grenov (A)

Department of Systems Immunology, Weizmann Institute of Science, Rehovot, 7610001, Israel.

Neta Gurwicz (N)

Department of Systems Immunology, Weizmann Institute of Science, Rehovot, 7610001, Israel.

Meital Kupervaser (M)

De Botton Institute for Proteomics, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Bon Ham Yip (BH)

Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.

Matteo Iannacone (M)

Vita-Salute San Raffaele University and Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Gur Yaari (G)

Faculty of Engineering, Bar Ilan University, Ramat Gan, 52900, Israel.

John D Crispino (JD)

Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, 38105, USA.

Ziv Shulman (Z)

Department of Systems Immunology, Weizmann Institute of Science, Rehovot, 7610001, Israel. ziv.shulman@weizmann.ac.il.

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Classifications MeSH