Metabolic strategies used by long-lived bone marrow plasma cells (P1474)

Abstract

Abstract Maintaining effective humoral immunity is an important aspect of healthy aging and the goal of most vaccines. Evidence from multiple laboratories agrees that long-lived humoral immunity derives from long-lived plasma cells (LLPC) that reside in the bone marrow. Because serum antibodies have a relatively short half-life and must be constantly produced, an urgent need is a clearer understanding of how LLPC maintain secretion of protective antibodies for years or a lifetime. PC secrete an estimated 1000 molecules of antibodies/sec, and some investigators make a compelling argument that the only recourse for a PC is a short lifespan, limited by oxidative and proteosomal stress. Our work begins to address how these important cells survive the extreme metabolic demands of constant antibodies secretion that is essential to lasting, protective immunity. We identified PC using the fluorescent probe ER Tracker - as highly-secretory cells, PC have large amounts of rough ER. In parallel, we stained cells with a reduced MitoTracker probe that fluoresces upon oxidation in respiring mitochondria. Our data show that ER Tracker-hi cells were found in both MitoTracker-hi and -lo populations, suggesting PC may use different metabolic strategies: aerobic respiration and glycolysis. Further studies will assess what governs each metabolic strategy, providing a deeper understanding of the cellular metabolic phenotype of long-lived plasma cells.