Myeloid Cell Regulation of Plasma cell engraftment into Bone Marrow

Abstract Vaccinations are one of the most cost-efficient and effective public health programs for combating infectious diseases such as malaria. One of the challenges, however, is that the longevity of antibody titers to vaccines varies greatly, requiring multiple boosts, especially among older populations. Antibody secreting cells (ASCs) are most responsible for antibody production. A sub-population of ASCs, known as long-lived PCs (LLPCs) found in the bone marrow (BM) are particularly important for maintaining antibody levels for a lifetime. LLPCs are unique, in that they are non-dividing but can survive for decades, and they also produce high-affinity antibodies which provide the best protection. Their survival is thought to depend on neighboring cells provide survival signals and protect these LLPCs from death, called niche. This niche is poorly understood and in particular, the organization and dynamics of the structure are unknown. Using intravital imaging in the BM, we have also found that newly-minted ASCs generated by immunization are colocalized with a subpopulations of myeloid cells. Based on our preliminary data, we hypothesize that these myeloid cells regulate engraftment ASCs in the BM. In this proposal, we seek to understand the underlying molecular mechanisms controlling this interaction. By analyzing this process in great detail, we will devise a new way to improve the response of all humoral-based vaccinations by improving ASC engraftment, potentially leading to more long-term survival of ASCs in the BM.