Abstract: Human long-lived plasma cells (LLPCs) are responsible for the durability of life-long protection from vaccines. Our studies will address fundamental processes underlying the development, maturation and survival of human plasma cells with the final goal of determining the impact of different factors and tissue niches in the generation and durability of LLPC. We will identify if the bone marrow (BM) niche is the one and only long-lived reservoir of if the human spleen also contains niches to support LLPC. We will also unravel the complex molecular mechanisms of STAT3 and CD74 signaling in the early generation of antibody secreting cells (ASC) located in the lymph node (LN) germinal centers (GC) which are released into the blood circulation to eventually migrate to BM and possibly splenic microniches to mature into LLPC.