Biochemical Mechanisms for Sustained Humoral Immunity

The project centers on the hypothesis that long-lived plasma cells in bone marrow obtain requisite signals to maintain antibody secretion and avoid cell death by sensing extracellular ATP (eATP) with a purinergic receptor known as P2rX4. It is further hypothesized that eATP is produced locally in the bone marrow for plasma cells by osteoblastic cells via the gap junction protein known as Panx3. Inhibition of P2rX4 or Panx3 function is predicted to cause the depletion of long-lived plasma cells and reduce serum antibody titers. The work will define cell intrinsic P2rX4-regulated outcomes for newborn and long-lived plasma cells, and define cell extrinsic sources and outcomes for eATP/Panx3 regulation of long-lived plasma cells. The long-term objective is to develop strategies to effectively and specifically disable or deplete problematic plasma cells.