Plasma Cell Priming

浆细胞启动

• 批准号: 9403332
• 负责人: David M Allman
• 金额: $ 24.15万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9403332
• 关键词: Address; Antibodies; Apoptotic; Autoantibodies; Autoimmune Diseases; Autoimmunity; Automobile Driving; B cell differentiation; B-Lymphocytes; BCL1 Oncogene; Bacteria; Biochemical; Biochemical Pathway; Biological Markers; Blood; Cell Count; Cell division; Cells; Couples; Cues; Data; Ensure; Evaluation; Event; FRAP1 gene; Family; Gene Deletion; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Generations; Genes; Goals; Host Defense; Immunity; In Situ; Kinetics; Knowledge; Lupus; Mediating; Mitosis; Molecular; Pathogenicity; Phase; Phosphotransferases; Plasma Cells; Play; Population; Positioning Attribute; Process; Proteins; Receptor Signaling; Rest; Role; Signal Pathway; Signal Transduction; Sinus; Spleen; TSC1 gene; Testing; Therapeutic; Transcript; Transgenes; Translating; Translations; Up-Regulation; Work; XBP1 gene; adenoviral-mediated; combat; cytokine; differentiated B cell; experimental study; extracellular; in vitro Model; in vivo; insight; mTOR inhibition; novel strategies; plasma cell differentiation; programs; receptor; receptor expression; response; transcription factor; transcriptome sequencing

Project summary The cellular and molecular events underlying the generation of self-reactive antibodies in autoimmunity remain poorly understood. Notably, marginal zone (MZ) B cells are enriched for self-reactive B cells, and are known to generate antibody-secreting plasma cells exceptionally quickly compared to other B cells. This R21 project centers on understanding the molecular mechanisms through which MZ B cells generate plasma cells with accelerated kinetics, with a focus on defining extracellular cues and associated intracellular signaling pathways that prime MZ B cells for differentiation. The central hypothesis guiding this work is that the mTOR/mTORC1 kinase, an emerging biomarker in lupus and related autoimmune diseases, couples BAFF-receptor signaling and expression of relevant plasma cell genes to facilitate rapid induction of antibody synthesis. To test this hypothesis we will: 1) Define the role of mTOR/mTORC1 signaling in plasma cell priming, and 2) Explore the identity of extracellular inputs driving plasma cell priming in situ. These studies will enhance knowledge of the processes underlying the generation of all plasma cells including those secreting pathogenic self-reactive antibodies.

项目总结