Human Plasma Cell Maturation & Maintenance through CD138, TNFRSF, and Modulation of Ig Secretion

Abstract: Human long-lived plasma cells (LLPC) reside in the bone marrow (BM) and are responsible for the long-term maintenance of serum antibody levels. The BM microniche provides important factors to fundamentally transform early-minted antibody secreting cells (ASC) into LLPC for which CD138 and BCMA - a member of the TNF receptor superfamily (TNFRSF) - play an important role. In this application, we explore old and new CD138 binding factors in the BM microniche and long-established and newly discovered TNFRSF members in the development of LLPC, as well as understanding how modulating the high energy function of antibody secretion determines LLPC survival. If successful, this application will provide the basic mechanisms important for durable vaccine design.