Igh locus function in immunosenescent mice
免疫衰老小鼠中的 Igh 基因座功能
基本信息
- 批准号:10303603
- 负责人:
- 金额:$ 23.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-11 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:2019-nCoV3-DimensionalAdultAgeAntibody RepertoireAntibody ResponseB-Cell DevelopmentB-LymphocytesBindingBiological AssayBiological ModelsBone MarrowCOVID-19COVID-19 mortalityCOVID-19 susceptibilityCell LineCell physiologyCellsChIP-seqChromatinClinicalCommunicable DiseasesCoronavirusDNADataDiseaseElementsEnhancersEpigenetic ProcessExonsFamilyFrequenciesFunctional disorderGenerationsGenesGenetic RecombinationIGH@ gene clusterImageImmuneImmune responseImmune systemImmunoglobulin Class SwitchingImmunoglobulin Switch RecombinationImmunoglobulinsImpairmentIndividualInfectious AgentInterventionLightLinkLymphopoiesisMature B-LymphocyteMediatingMolecular ConformationMusNucleic Acid Regulatory SequencesPatientsPeripheralPredispositionPublishingRegulatory ElementResolutionSeriesSiteTimeLineV(D)J RecombinationViraladaptive immune responseage relatedagedcell agehelix-loop-helix protein E47human old age (65+)immunosenescenceinsightmembermouse modelpandemic diseasepathogenprogenitorpromoterresponsesenescence
项目摘要
ABSTRACT
COVID-19 (coronavirus infectious disease 19) is now a global pandemic with over 49.1 million cases to
date. COVID-19 is caused by severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2, a member
of the coronavirus family. It is striking that eighty percent of COVID-19 related deaths occur in patients
aged 65 and over. Immune responses of aged adults undergo immunosenescence which expresses with
multiple age dependent changes. Immune senescence is linked to restricted Ig repertoire formation and
susceptibility to a variety of virally induced diseases. Older individuals are particularly vulnerable to a
range of new and emerging infectious agents perhaps as a result of a less diverse antibody repertoire.
However, to identify clinical interventions that mitigate the effects of immunosenescence it is critical to
characterize the underlying environmental and cell intrinsic mechanisms leading to the muted adaptive
immune responses. Here we propose an exploratory series of studies to examine the pre-selected Ig
repertoire in early and mature B cells in young and aged mice to establish whether repertoire deficiencies
observed in peripheral B cells of aged individuals originate, at least in part, from impaired V(D)J
recombination, class switch recombination, locus conformation and/or Igh enhancer function. Results
obtained from this exploratory project will shed light on whether a) limited Ig repertoire diversification
results from impaired Igh locus function during V(D)J recombination and class switch recombination, and
b) whether Igh locus dysfunction is cell intrinsic.
摘要
COVID-19(冠状病毒感染性疾病19)现在是一种全球大流行病,
约会COVID-19是由严重急性呼吸道综合征(SARS)-冠状病毒(CoV)-2引起的,
冠状病毒家族令人震惊的是,80%的COVID-19相关死亡发生在患者身上,
65岁及以上老年人的免疫应答经历免疫衰老,
多种年龄依赖性变化。免疫衰老与限制性IG库形成有关,
对各种病毒引起的疾病的易感性。老年人特别容易受到
一系列新的和正在出现的感染因子可能是由于抗体库的多样性较低。
然而,为了确定减轻免疫衰老影响的临床干预措施,
表征潜在的环境和细胞内在机制,导致静音适应
免疫反应。在这里,我们提出了一个探索性的一系列研究,以检查预先选定的IG
年轻和老年小鼠早期和成熟B细胞的谱系以确定谱系是否缺陷
在老年人的外周B细胞中观察到,至少部分来源于受损的V(D)J
在一些实施方案中,IgH增强子的功能可以是基因座重组、类别转换重组、基因座构象和/或IgH增强子功能。结果
从这个探索性项目中获得的信息将揭示a)有限的IG库多样化
由V(D)J重组和类别转换重组期间Igh基因座功能受损引起,和
B)Igh基因座功能障碍是否是细胞内在的。
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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Amy L Kenter其他文献
Amy L Kenter的其他文献
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{{ truncateString('Amy L Kenter', 18)}}的其他基金
Impact of novel enhancers on Igh repertoire diversity
新型增强子对 Igh 库多样性的影响
- 批准号:
10716628 - 财政年份:2023
- 资助金额:
$ 23.45万 - 项目类别:
Igh locus function in immunosenescent mice
免疫衰老小鼠中的 Igh 基因座功能
- 批准号:
10427437 - 财政年份:2021
- 资助金额:
$ 23.45万 - 项目类别:
Characterization of chromatin loops responsible for Igh locus contraction
负责 Igh 基因座收缩的染色质环的表征
- 批准号:
8873312 - 财政年份:2015
- 资助金额:
$ 23.45万 - 项目类别:
Role of MBD4 in double strand break formation during class switch recombination
MBD4 在类别转换重组过程中双链断裂形成中的作用
- 批准号:
8702378 - 财政年份:2014
- 资助金额:
$ 23.45万 - 项目类别:
Class switch recombination during early B cell development
早期 B 细胞发育过程中的类别转换重组
- 批准号:
8594576 - 财政年份:2013
- 资助金额:
$ 23.45万 - 项目类别:
Class switch recombination during early B cell development
早期 B 细胞发育过程中的类别转换重组
- 批准号:
8664344 - 财政年份:2013
- 资助金额:
$ 23.45万 - 项目类别:
Lymphocytes/Immune System:Cellular/Interactive Mechanism
淋巴细胞/免疫系统:细胞/相互作用机制
- 批准号:
7000871 - 财政年份:2005
- 资助金额:
$ 23.45万 - 项目类别:
Factors and DNA Motifs Involved in Ig Class Switch
参与 Ig 类别转换的因素和 DNA 基序
- 批准号:
6629967 - 财政年份:2003
- 资助金额:
$ 23.45万 - 项目类别:
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