TY - JOUR
T1 - B cell class switch recombination is regulated by DYRK1A through MSH6 phosphorylation
AU - Stoler-Barak, Liat
AU - Harris, Ethan
AU - Peres, Ayelet
AU - Hezroni, Hadas
AU - Kuka, Mirela
AU - Di Lucia, Pietro
AU - Grenov, Amalie
AU - Gurwicz, Neta
AU - Kupervaser, Meital
AU - Yip, Bon Ham
AU - Iannacone, Matteo
AU - Yaari, Gur
AU - Crispino, John D.
AU - Shulman, Ziv
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85150316366&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-37205-5
DO - 10.1038/s41467-023-37205-5
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C2 - 36927854
AN - SCOPUS:85150316366
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1462
ER -
