Epigenetic Control of Plasma Cell Differentiation

浆细胞分化的表观遗传控制

基本信息

批准号：
9105812
负责人：
David M Allman
金额：
$ 20万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-06 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9105812
关键词：
Address Adopted Agonist Antibodies Antigens Autoantibodies Autoimmune Diseases B Cell Proliferation B cell differentiation B-Cell Activation B-Lymphocyte Subsets B-Lymphocytes Cell Cycle Cell division Cells ChIP-seq Chromosome Positioning Clonal Expansion DNA Methylation Epigenetic Process Event Exhibits Gene Expression Generations Genes Genetic Transcription Genome Goals Health Histone Acetylation Immunity Immunoglobulin-Secreting Cells In Vitro Kinetics Knowledge Lead Life Link Mediating Memory Memory B-Lymphocyte Mitosis Modification Molecular Nuclear Structure Nucleic Acid Regulatory Sequences Pattern Plasma Cells Polymerase Process Proliferating Published Comment RNA Polymerase II Recording of previous events Rest Role Signal Transduction Spleen System Testing Therapeutic Time Transcription Repressor/Corepressor Transgenic Organisms Work base bisulfite sequencing combat cytokine epigenetic regulation experience histone methylation histone modification in vivo inhibitor/antagonist insight methylation pattern plasma cell differentiation prevent programs promoter research study transcription factor

项目摘要

DESCRIPTION (provided by applicant): The epigenetic and transcriptional events controlling the differentiation of antibody- secreting plasma cells (PCs) from activated B cells remain unclear. Furthermore, though memory B cells and naive B cells in the marginal zone (MZ) of the spleen are known to generate PCs faster than the bulk of naive B cells, how PC inductive signals integrate with other processes such as cell division to drive PC differentiation in distinc B cell subsets is unknown. The main goals of this R21 application are to understand how epigenetic modifiers control the kinetics of early PC differentiation for MZ and memory B cells and the role of cell division in these processes with an emphasis on the regulated expression of the PC-required transcription factor Blimp1. To this end we will: 1) Define the role of cell divisin in PC differentiation, and 2) Define the epigenetic regulation of the Blimp1 locus upon B cell activation and selection. These studies will enhance knowledge of the processes underlying the generation of all PCs including pathogenic PCs secreting self-reactive antibodies.

描述（由适用提供）：控制抗体分泌浆细胞（PC）与活化B细胞的分化的表观遗传和转录事件尚不清楚。此外，尽管已知脾脏边缘区（MZ）中的记忆B细胞和幼稚的B细胞比大部分幼稚B细胞更快地生成PCS，但未知的PC诱导信号如何与其他过程（例如细胞分裂）集成以驱动DISTINC B细胞中的PC分化的PC诱导信号是未知的。该R21应用的主要目标是了解表观遗传修饰器如何控制MZ和记忆B细胞的早期PC分化动力学以及细胞分裂在这些过程中的作用，并重点是PC所需的转录因子Blimp1的调节表达。为此，我们将：1）定义细胞分裂在PC分化中的作用，以及2）在B细胞激活和选择时定义Blimp1基因座的表观遗传调节。这些研究将增强对所有PC产生的过程的知识，包括分泌自反应抗体的病原PC。