| First Author | Tang H | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 5 | Pages | 104209 |
| PubMed ID | 35494252 | Mgi Jnum | J:333667 |
| Mgi Id | MGI:7276013 | Doi | 10.1016/j.isci.2022.104209 |
| Citation | Tang H, et al. (2022) IP3R-mediated Ca(2+) signaling controls B cell proliferation through metabolic reprogramming. iScience 25(5):104209 |
| abstractText | Emerging evidence shows that metabolic regulation may be a critical mechanism in B cell activation and function. As targets of several most widely used immunosuppressants, Ca(2+) signaling and calcineurin may play an important role in regulating B cell metabolism. Here, we demonstrate that IP3R-mediated Ca(2+) signaling and calcineurin regulate B cell proliferation and survival by activating metabolic reprogramming in response to B cell receptor (BCR) stimulation. Both IP3R-triple-knockout (IP3R-TKO) and calcineurin inhibition dramatically suppress the metabolic switch in oxidative phosphorylation and glycolysis of stimulated B cells through regulation of glucose uptake, glycolytic enzyme expression, and mitochondrial remodeling, leading to impaired cell-cycle entry and survival. In addition, IP3R-Ca(2+) acts as a master regulator of the calcineurin-MEF2C-Myc pathway in driving B cell metabolic adaptations. As genetic defects of IP3Rs were recently identified as a new class of inborn errors of immunity, these results have important implications for understanding the pathogenesis of such diseases. |
