| First Author | Jellusova J | Year | 2017 |
| Journal | Nat Immunol | Volume | 18 |
| Issue | 3 | Pages | 303-312 |
| PubMed ID | 28114292 | Mgi Jnum | J:301981 |
| Mgi Id | MGI:6142656 | Doi | 10.1038/ni.3664 |
| Citation | Jellusova J, et al. (2017) Gsk3 is a metabolic checkpoint regulator in B cells. Nat Immunol 18(3):303-312 |
| abstractText | B cells predominate in a quiescent state until an antigen is encountered, which results in rapid growth, proliferation and differentiation of the B cells. These distinct cell states are probably accompanied by differing metabolic needs, yet little is known about the metabolic control of B cell fate. Here we show that glycogen synthase kinase 3 (Gsk3) is a metabolic sensor that promotes the survival of naive recirculating B cells by restricting cell mass accumulation. In antigen-driven responses, Gsk3 was selectively required for regulation of B cell size, mitochondrial biogenesis, glycolysis and production of reactive oxygen species (ROS), in a manner mediated by the co-stimulatory receptor CD40. Gsk3 was required to prevent metabolic collapse and ROS-induced apoptosis after glucose became limiting, functioning in part by repressing growth dependent on the myelocytomatosis oncoprotein c-Myc. Notably, we found that Gsk3 was required for the generation and maintenance of germinal center B cells, which require high glycolytic activity to support growth and proliferation in a hypoxic microenvironment. |
