GLUCOSE AND AMINO ACID CATABOLISM IN PLASMA CELL BIOLOGY

浆细胞生物学中的葡萄糖和氨基酸分解代谢

基本信息

批准号：
10530743
负责人：
Deepta Bhattacharya
金额：
$ 7.5万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-12-13 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10530743
关键词：
Amino Acids Antibodies Antibody Formation Biological Models Catabolism Cell Survival Cell membrane Cell physiology Cells Cellular biology Data Energy-Generating Resources Equilibrium Genetic Glucose Glycolysis Goals Hexosamines Humoral Immunities Immunity Immunoglobulin-Secreting Cells Infection Knock-out Lactic Acidosis Length Longevity Metabolic Metabolic Pathway Metabolism Mitochondria Modeling Non-Malignant Nutrient Oxidation-Reduction Oxidative Phosphorylation Oxides PERK kinase Pathway interactions Phosphorylation Physiological Plasma Cells Pyruvate Reporting Respiration Signal Transduction Testing Time Vaccination Vaccines cell type endoplasmic reticulum stress extracellular glucose uptake glycosylation improved in vivo interest pathogen prevent programs pyruvate carrier respiratory stable isotope uptake vaccine-induced immunity

项目摘要

The usage of metabolic pathways is tailored to meet the specific functions and demands of a given cell type. Of particular interest is how metabolism supports the survival and antibody secretion of long-lived cells, the primary cell type that is responsible for humoral immunity. Using plasma cells as a model system, we will define how glucose and amino acid uptake supports long-term persistence of these antibody-secreting cells. In preliminary data, we demonstrate that long-lived plasma cells import far more glucose than do their short-lived counterparts. Glucose is primarily used to glycosylate antibodies, but a portion of this glucose can be used for glycolysis, and the resultant pyruvate imported into the mitochondria. Short-lived plasma cells do not have this capacity. We propose to define the metabolic fates of pyruvate and explain why this pathway is important in long-lived plasma cells. We also propose to define how long-lived plasma cells balance enhanced antibody production with nutrient uptake and ER stress. Finally, we seek to define the physiological signals that promote plasma cell metabolic programs following vaccination. The application heavily emphasizes new genetic and in vivo approaches to define, report, and functionally test critical metabolic pathways in a cell type critical for humoral immunity.

定制代谢途径的使用以满足给定细胞类型的特定功能和需求。特别令人感兴趣的是，新陈代谢如何支持长寿命细胞的生存和抗体分泌，这是负责体液免疫的主要细胞类型。使用浆细胞作为模型系统，我们将定义葡萄糖和氨基酸摄取如何支持这些分泌抗体分泌细胞的长期持久性。在初步数据中，我们证明了长寿命的浆细胞进口的葡萄糖要比其短寿命的葡萄糖要多得多。葡萄糖主要用于糖基化抗体，但该葡萄糖的一部分可用于糖酵解，并且所得的丙酮酸进口到线粒体中。短寿命的浆细胞没有这种能力。我们建议定义丙酮酸的代谢命运，并解释为什么该途径在长寿命的浆细胞中很重要。我们还建议定义寿命长的浆细胞与营养摄取和ER应激之间的增强抗体的产生。最后，我们试图定义疫苗接种后促进血浆细胞代谢程序的生理信号。该应用严重强调了新的遗传和体内方法，以定义，报告和在功能上测试对体液免疫至关重要的细胞类型的关键代谢途径。