Understanding Survival of Human Bone Marrow Long-Lived Plasma Cells

了解人类骨髓长寿浆细胞的存活

基本信息

批准号：
9008805
负责人：
Frances Eun-Hyung Lee
金额：
$ 39万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-01 至 2020-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9008805
关键词：
Adult Amino Acids Angiogenic Factor Antibodies Antibody Formation Antigens Aspirate substance Autoimmunity Autophagocytosis Autophagosome Biochemical Pathway Blood Bone Marrow CD19 gene CD28 gene Cell Communication Cell Culture Techniques Cell Survival Cells Chromatin Coculture Techniques Data Deamination Diagnostic tests Disease FRAP1 gene Flow Cytometry Generations Genes Goals Golgi Apparatus Growth Hepatitis A Human Hypersensitivity Hypoxia Immunization In Vitro Infection Intrinsic factor Life Link Lipids Longevity Lysosomes Maintenance Measures Mesenchymal Metabolic Metabolic Pathway Metabolism Methods Modeling Molecular Monoclonal Antibodies Morphology Multiple Myeloma Pathway interactions Pharmaceutical Preparations Plasma Cells Plasmablast Property Proteins Proteomics RNA Research Personnel Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis Serum Sorting - Cell Movement Source Specificity Stromal Cells Testing Transplantation VEGFC gene Vaccination Vaccine Adjuvant Vaccines Vascular Endothelial Growth Factors Viral Work Yellow Fever bevacizumab design differential expression fatty acid oxidation glucose uptake imprint inhibitor/antagonist insight novel novel diagnostics oncology oxidation programs public health relevance response transcriptome vaccine response

项目摘要

DESCRIPTION (provided by applicant): Long-lived plasma cells (LLPC) sustain protective antibody production for a lifetime but the identity of the cellular source of human LLPC has eluded us for decades. In our lab, we have definitively linked the long-lived viral serum antibody source to a single cellular compartment within the human bone marrow (BM). The PC specificities concentrate in these unique long-lived viral specificities from exposures that occurred over 40-60 years ago. In this application, we will study the survival mechanisms of human BM LLPC by (1) understanding the ontogeny and survival of the short-lived PC and the LLPC, (2) testing the intrinsic molecular mechanisms of LLPC survival, and (3) defining the unique metabolic signatures of LLPC. The significance of this work is several-fold from understanding the means of generation to the mechanisms of maintenance (or survival) of human LLPC. It will provide insights to designing vaccine adjuvants, developing novel targets of pathogenic plasma cells in diseases such as autoimmunity, allergy, and transplantation (sparing protective LLPC), and offering novel diagnostic testing and drug pathways to treat multiple myeloma (oncology).

描述（由适用提供）：长寿命的浆细胞（LLPC）终生维持受保护的抗体产生，但是人类LLPC的细胞来源的身份已经使我们避免了数十年。在我们的实验室中，我们将长寿命的病毒血清抗体源与人骨髓（BM）中的单个细胞隔室联系起来。 PC规格集中在这些独特的长寿命病毒规格上，来自40 - 60年前发生的暴露。在此应用中，我们将通过（1）了解短寿命PC和LLPC的个体发育和存活，研究人类BM LLPC的生存机制，（2）测试LLPC的固有分子机制，以及（3）定义LLPC的独特代谢特征。这项工作的意义是从了解生成手段到人类LLPC的维持（或生存）机制的几倍。它将为设计疫苗佐剂，开发诸如自身免疫性，过敏和移植（备用受保护的LLPC）等疾病中的致病性血浆细胞的新靶标提供见解，并为治疗多发性骨髓瘤（肿瘤学）提供新颖的诊断测试和药物途径。