| First Author | Stoler-Barak L | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 1462 |
| PubMed ID | 36927854 | Mgi Jnum | J:338911 |
| Mgi Id | MGI:7445893 | Doi | 10.1038/s41467-023-37205-5 |
| Citation | Stoler-Barak L, et al. (2023) B cell class switch recombination is regulated by DYRK1A through MSH6 phosphorylation. Nat Commun 14(1):1462 |
| abstractText | 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. |
