Human Vaccine Durability using Integrated Bioinformatics and a Novel in vitro Bone Marrow Mimic

使用整合生物信息学和新型体外骨髓模拟物的人类疫苗耐久性。 摘要： 长寿命浆细胞（LLPC）维持保护性抗体产生达一生，并且是免疫调节的细胞基础。 疫苗的持久性和需要骨髓（BM）的微粒来维持生存。在我们的实验室里， 明确地将长寿病毒血清抗体与健康人体内的BM细胞区室联系起来 BM（CD19-CD38hiCD138+）PC亚群，从而建立LLPC区室。我们还开发了 体外BM微环境培养，模拟BM微环境以维持PC存活。在本申请中，我们 计划（1）使用这种新的体外BM模拟物开发疫苗耐久性的新的体外生物标志物， 剖析长效疫苗的早期血液ASC的机制，急性病毒感染，与短期疫苗相比， （2）在疫苗接种后早期鉴定血液中LLPC前体的独特身份，以及（3） 研究LLPC在系统性红斑狼疮疾病模型中产生的机制， 其特征在于高水平的长寿命抗体和丰富的LLPC。总之，这些研究将 区分LLPC产生和免疫后维持的细胞和分子程序。

Human Vaccine Durability using Integrated Bioinformatics and a Novel in vitro Bone Marrow Mimic. Abstract: Long-lived plasma cells (LLPC) sustain protective antibody production for a lifetime and are the cellular basis of vaccine durability and require the bone marrow (BM) microniche to sustain survival. In our lab, we have definitively linked the long-lived viral serum antibodies to the BM cellular compartment within the healthy human BM (CD19-CD38hiCD138+) PC subset thereby establishing the LLPC compartment. We have also developed in vitro BM microniche cultures that mimic the BM microenvironment to sustain PC survival. In this application, we plan (1) to develop a novel in vitro biomarker of vaccine durability using this novel in vitro BM mimic and to dissect the mechanisms of early blood ASC of long-lived vaccines, acute viral infections, compared to short-lived vaccines, (2) to identify the unique identity of LLPC precursors in the blood early after vaccination, and (3) to study mechanisms of LLPC generation in disease models of Systemic Lupus Erythematosis which is characterized by high levels of long-lived antibodies and an abundance of LLPC. In summary, these studies will distinguish the cellular and molecular programs of LLPC generation and maintenance after immunization.