| First Author | Schoeler K | Year | 2019 |
| Journal | Cell Death Differ | Volume | 26 |
| Issue | 12 | Pages | 2551-2567 |
| PubMed ID | 30894677 | Mgi Jnum | J:298423 |
| Mgi Id | MGI:6480100 | Doi | 10.1038/s41418-019-0318-5 |
| Citation | Schoeler K, et al. (2019) CHK1 dosage in germinal center B cells controls humoral immunity. Cell Death Differ 26(12):2551-2567 |
| abstractText | Germinal center (GC) B cells are among the fastest replicating cells in our body, dividing every 4-8 h. DNA replication errors are intrinsically toxic to cells. How GC B cells exert control over the DNA damage response while introducing mutations in their antibody genes is poorly understood. Here, we show that the DNA damage response regulator Checkpoint kinase 1 (CHK1) is essential for GC B cell survival. Remarkably, effective antibody-mediated immunity relies on optimal CHK1 dosage. Chemical CHK1 inhibition or loss of one Chk1 allele impairs the survival of class-switched cells and curbs the amplitude of antibody production. Mechanistically, active B cell receptor signaling wires the outcome of CHK1-inhibition towards BIM-dependent apoptosis, whereas T cell help favors temporary cell cycle arrest. Our results predict that therapeutic CHK1 inhibition in cancer patients may prove potent in killing B cell lymphoma and leukemia cells addicted to B cell receptor signaling, but will most likely dampen humoral immunity. |
