| First Author | Utley A | Year | 2020 |
| Journal | Cell Rep | Volume | 31 |
| Issue | 12 | Pages | 107815 |
| PubMed ID | 32579940 | Mgi Jnum | J:308384 |
| Mgi Id | MGI:6714406 | Doi | 10.1016/j.celrep.2020.107815 |
| Citation | Utley A, et al. (2020) CD28 Regulates Metabolic Fitness for Long-Lived Plasma Cell Survival. Cell Rep 31(12):107815 |
| abstractText | Durable humoral immunity against epidemic infectious disease requires the survival of long-lived plasma cells (LLPCs). LLPC longevity is dependent on metabolic programs distinct from short-lived plasma cells (SLPCs); however, the mechanistic basis for this difference is unclear. We have previously shown that CD28, the prototypic T cell costimulatory receptor, is expressed on both LLPCs and SLPCs but is essential only for LLPC survival. Here we show that CD28 transduces pro-survival signaling specifically in LLPCs through differential SLP76 expression. CD28 signaling in LLPCs increased glucose uptake, mitochondrial mass/respiration, and reactive oxygen species (ROS) production. Unexpectedly, CD28-mediated regulation of mitochondrial respiration, NF-kappaB activation, and survival was ROS dependent. IRF4, a target of NF-kappaB, was upregulated by CD28 activation in LLPCs and decreased IRF4 levels correlated with decreased glucose uptake, mitochondrial mass, ROS, and CD28-mediated survival. Altogether, these data demonstrate that CD28 signaling induces a ROS-dependent metabolic program required for LLPC survival. |
