Epigenetic Control of Plasma Cell Differentiation

浆细胞分化的表观遗传控制

• 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
• 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

 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(由申请人提供)：控制抗体分泌浆细胞(PC)从激活的B细胞分化的表观遗传和转录事件仍不清楚。此外，虽然已知脾边缘带(MZ)的记忆B细胞和幼稚B细胞比大部分幼稚B细胞更快地产生PC，但PC诱导信号如何与其他过程(如细胞分裂)相结合来驱动远端B细胞亚群中的PC分化尚不清楚。该R21应用的主要目标是了解表观遗传修饰物如何控制MZ和Memory B细胞早期PC分化的动力学，以及细胞分裂在这些过程中的作用，重点是PC所需的转录因子Blimp1的调控表达。为此，我们将：1)确定细胞分裂素在PC分化中的作用；2)确定Blimp1基因座对B细胞激活和选择的表观遗传调节。这些研究将加强对所有PC产生的潜在过程的了解，包括分泌自我反应性抗体的致病PC。