Project 3: Role of Cellular Senescence in long-lived plasma cell generation Abstract: Human long-lived plasma cells (LLPC) are important in the maintenance of protective serum antibodies. The mechanisms of how LLPC are generated and sustained are not well elucidated. These bone marrow resident cells are terminally differentiated, nondividing, and refractory to apoptosis yet they are capable of secreting antibodies for a lifetime. Exodus from cell cycle and resistance to apoptosis are major hallmarks of cellular senescence. In this application, we will understand the role of cellular senescence in LLPC maturation transcriptionally and epigenetically through single cell analysis. We will also dissect the unique senescence pathways that are needed for survival; then finally we will identify the unique components of the BM microniche that plays a role in survival and senescence.