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:
- 金额:$ 20万
- 依托单位:
- 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:
- 关键词:AddressAdoptedAgonistAntibodiesAntigensAutoantibodiesAutoimmune DiseasesB Cell ProliferationB cell differentiationB-Cell ActivationB-Lymphocyte SubsetsB-LymphocytesCell CycleCell divisionCellsChIP-seqChromosome PositioningClonal ExpansionDNA MethylationEpigenetic ProcessEventExhibitsGene ExpressionGenerationsGenesGenetic TranscriptionGenomeGoalsHealthHistone AcetylationImmunityImmunoglobulin-Secreting CellsIn VitroKineticsKnowledgeLeadLifeLinkMediatingMemoryMemory B-LymphocyteMitosisModificationMolecularNuclear StructureNucleic Acid Regulatory SequencesPatternPlasma CellsPolymeraseProcessProliferatingPublished CommentRNA Polymerase IIRecording of previous eventsRestRoleSignal TransductionSpleenSystemTestingTherapeuticTimeTranscription Repressor/CorepressorTransgenic OrganismsWorkbasebisulfite sequencingcombatcytokineepigenetic regulationexperiencehistone methylationhistone modificationin vivoinhibitor/antagonistinsightmethylation patternplasma cell differentiationpreventprogramspromoterresearch studytranscription 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。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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David M Allman其他文献
David M Allman的其他文献
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针对同种异体反应性浆细胞的蛋白酶体
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10652461 - 财政年份:2020
- 资助金额:
$ 20万 - 项目类别:
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