CD28 Regulates Metabolic Fitness for Long-Lived Plasma Cell Survival

• DOI: 10.1016/j.celrep.2020.107815
• Publication Date: 2020-06-23T14:37:49Z
• Authors: Adam Utley; Colin Chavel; Shivana Lightman; G. Aaron Holling; James Cooper; Peng Peng; Wensheng Liu; Benjamin G. Barwick; Catherine M. Gavile; Orla Maguire; Megan Murray-Dupuis; Cheryl Rozanski; Martha S. Jordan; Taku Kambayashi; Scott H. Olejniczak; Lawrence H. Boise; Kelvin P. Lee
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Cell Survival; Cell Respiration; Plasma Cells; Bone Marrow Cells; Article; Mitochondria; Mice, Inbred C57BL; 03 medical and health sciences; Glucose; CD28 Antigens; Interferon Regulatory Factors; Animals; Humans; Female; Reactive Oxygen Species; Spleen; Signal Transduction

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 (SLPCs); however, mechanistic basis for this difference unclear. We have previously shown that CD28, prototypic T cell costimulatory receptor, expressed both LLPCs and SLPCs but essential only survival. Here we show CD28 transduces pro-survival signaling specifically in through differential SLP76 expression. increased glucose uptake, mitochondrial mass/respiration, reactive oxygen species (ROS) production. Unexpectedly, CD28-mediated regulation respiration, NF-κB activation, was ROS dependent. IRF4, a target NF-κB, upregulated by activation decreased IRF4 levels correlated with mass, ROS, Altogether, these data demonstrate induces ROS-dependent program required