Contribution of ASC Dynamics to Survival within the Bone Marrow

摘要 体液免疫是世界范围内所有疫苗接种活动的基础，也是最有效的疫苗接种方式之一。 公共卫生进步来减少疾病。体液免疫的关键是发展和长期 长寿命抗体分泌细胞（LLASC）的存活。LLASC存在于骨髓（BM）中，并且可以赋予 对特定病原体的终生保护。然而，一些疫苗接种只能诱导暂时的 免疫（几个月到几年）。因此，了解LLASC如何生存可以深入了解如何改善 疫苗。 ASC被认为停靠在一个静态的支持性小生境中，在那里它们可以接收促生存信号（IL-6，APRIL） 并产生抗体。ASC-niche的研究已经暗示了许多支持ASCs的细胞类型， 它们产生促存活细胞因子的能力以及它们在静态共聚焦图像中与ASC的紧密接近。 然而，这些研究并没有解决ASC如何在其生态位内动态地相互作用，也没有解决ASC如何在其生态位内动态地相互作用。 新产生的或LLASC）竞争利基提供的有限资源。因此，如何动态 影响ASC竞争、生存和寿命的因素尚不清楚。本项目旨在了解如何 ASC的动力学影响它们在BM中的竞争和存活。 在这个项目中，我将评估ASCs如何在BM环境中相互作用。我将联合收割机 显微镜与新的和经典的功能研究，以研究促进动态ASC的因素 在他们的BM生态位内的相互作用。我将确定有助于ASC动态的因素，并剖析如何 动力学影响ASC在BM中的长期存活和保留。这项工作将产生新的见解， BM的驻留细胞如何与其特定的小生境相互作用，并更好地了解BM ASC 利基

Abstract Humoral immunity is the basis of all worldwide vaccination campaigns and has been one of the most effective public health advancements to curtail disease. Critical to humoral immunity is the development and long term survival of long-lived antibody secreting cells (LLASCs). LLASCs reside in the bone marrow (BM) and can confer protection towards specific pathogens for a lifetime. However, some vaccinations can only induce temporary immunity (months to a few years). Therefore, understanding how LLASCs survive can yield insight into improving vaccines. ASCs are thought to dock into a static, supportive niche where they can receive pro survival signals (IL-6, APRIL) and produce antibody. Studies of the ASC-niche have implicated a number of cell types in supporting ASCs due to their ability to produce pro survival cytokines and their close proximity to ASCs in static, confocal images. However, these studies do not address how ASCs dynamically interact within their niche nor how ASCs (either newly generated or LLASCs) compete for the limited resources provided by the niche. Therefore, how dynamics affect ASC competition, survival, and factor into longevity is not known. This project seeks to understand how the dynamics of ASCs affects their competition and survival in the BM. In this project I will assess how ASCs interact within the BM environment. I will combine intravital two photon microscopy with novel and classical functional studies to study the factors that promote dynamic ASC interactions within their BM niche. I will determine the factors that contribute to ASC dynamics and dissect how the dynamics affects long-term survival and retention of ASCs in the BM. This work will yield new insights into how resident cells of the BM interact with their specific niches and to a better understanding of the BM ASC niche.