| First Author | Berry CT | Year | 2020 |
| Journal | Cell Rep | Volume | 31 |
| Issue | 2 | Pages | 107474 |
| PubMed ID | 32294437 | Mgi Jnum | J:323545 |
| Mgi Id | MGI:6715289 | Doi | 10.1016/j.celrep.2020.03.038 |
| Citation | Berry CT, et al. (2020) BCR-Induced Ca(2+) Signals Dynamically Tune Survival, Metabolic Reprogramming, and Proliferation of Naive B Cells. Cell Rep 31(2):107474 |
| abstractText | B cell receptor (BCR) engagement induces naive B cells to differentiate and perform critical immune-regulatory functions. Acquisition of functional specificity requires that a cell survive, enter the cell cycle, and proliferate. We establish that quantitatively distinct Ca(2+) signals triggered by variations in the extent of BCR engagement dynamically regulate these transitions by controlling nuclear factor kappaB (NF-kappaB), NFAT, and mTORC1 activity. Weak BCR engagement induces apoptosis by failing to activate NF-kappaB-driven anti-apoptotic gene expression. Stronger signals that trigger more robust Ca(2+) signals promote NF-kappaB-dependent survival and NFAT-, mTORC1-, and c-Myc-dependent cell-cycle entry and proliferation. Finally, we establish that CD40 or TLR9 costimulation circumvents these Ca(2+)-regulated checkpoints of B cell activation and proliferation. As altered BCR signaling is linked to autoimmunity and B cell malignancies, these results have important implications for understanding the pathogenesis of aberrant B cell activation and differentiation and therapeutic approaches to target these responses. |
