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）与活化 B 细胞分化的表观遗传和转录事件仍不清楚。此外，尽管已知脾脏边缘区 (MZ) 中的记忆 B 细胞和幼稚 B 细胞比大量幼稚 B 细胞更快地生成 PC，但 PC 诱导信号如何与细胞分裂等其他过程整合以驱动不同 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剂如何控制 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，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，2) 定义 Blimp1 位点对 B 细胞激活和选择的表观遗传调控。这些研究将增强对所有 PC 生成过程的了解，包括分泌自身反应性抗体的致病性 PC。