CD138 Regulates Competition of Antibody Secreting Cells for Survival

Abstract Vaccinations are one of the most beneficial and cost-effective public health programs. Unfortunately, many vaccines need repeated boosting to maintain antibody levels. In particular, humoral responses are weaker in older adults for a number of reasons. For example, immunization with live measles virus produces antibody titers that are maintained for 50 years, while protein vaccines, such as tetanus or anthrax toxin, require routine booster shots every five years to maintain antibody titer. The reasons for this variability are poorly understood, but as steady-state antibody titers are directly dependent on long- lived antibody secreting cells (LLASCs), these cells may be dying over time. The factors that control LLASC survival in the are poorly understood, but are critically important for all humoral-based vaccines. Survival of LLASCs is chiefly mediated by soluble cytokines, such as APRIL, CXCL12 in the BM by resident cells. The presentation of these factors and the organization of the niche that supports these cells is unclear. In this proposal, we explore how LLASC retention in clusters or niches, their cellular dynamics controls their survival and competition, and how the niche is organized and maintained. These pathways can regulate longevity of humoral responses.