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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：
Amy L Kenter
金额：
$ 23.45万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
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：
https://reporter.nih.gov/project-details/10303603
关键词：
2019-nCoV 3-Dimensional Adult Age Antibody Repertoire Antibody Response B-Cell Development B-Lymphocytes Binding Biological Assay Biological Models Bone Marrow COVID-19 COVID-19 mortality COVID-19 susceptibility Cell Line Cell physiology Cells ChIP-seq Chromatin Clinical Communicable Diseases Coronavirus DNA Data Disease Elements Enhancers Epigenetic Process Exons Family Frequencies Functional disorder Generations Genes Genetic Recombination IGH@ gene cluster Image Immune Immune response Immune system Immunoglobulin Class Switching Immunoglobulin Switch Recombination Immunoglobulins Impairment Individual Infectious Agent Intervention Light Link Lymphopoiesis Mature B-Lymphocyte Mediating Molecular Conformation Mus Nucleic Acid Regulatory Sequences Patients Peripheral Predisposition Publishing Regulatory Element Resolution Series Site TimeLine V(D)J Recombination Viral adaptive immune response age related aged cell age helix-loop-helix protein E47 human old age (65+)immunosenescence insight member mouse model pandemic disease pathogen progenitor promoter response senescence

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