The role of Apobec3 enzymes in regulation of marginal zone B cells
The role of Apobec3 enzymes in regulation of marginal zone B cells
批准号:
8664346
负责人:
Anthony L Defranco
金额:
$19.75万
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-07-01 至 2016-06-30
关键词:
AffectAntibodiesAntigensApplications GrantsB-LymphocytesBiologicalBlood-Borne PathogensBone MarrowCell CountCell SeparationCellsComplementary DNADNADevelopmentEmployee StrikesEnvironmentEnzymesExogenous FactorsFamilyGene Expression ProfileGenesGenomeGoalsHealthHumanHuman GenomeImmune systemImmunoglobulin MInflammationInsertional MutagenesisInterferon ReceptorInterferonsIsoenzymesLymphocyteMalignant NeoplasmsMalpighian corpusclesMediatingMusPopulationProteinsRegulationRetroelementsRetrotransposonRetroviridaeRoleSpleenSplenic Red PulpT-LymphocyteTestingTransgenic Micedeep sequencingdesigninsightmacrophagemouse genomeresearch studyresponse
中文摘要
描述(由申请人提供):Apobec 3酶在边缘区B细胞调节中的作用Apobec 3酶是外源性和内源性逆转录因子(逆转录病毒和逆转录转座子)的限制性因子。内源性逆转录因子几乎占小鼠和人类基因组的一半,其中许多具有体细胞活性。它们通常散布在细胞基因中,因此与细胞基因沿着转录。不受限制的逆转录因子可以引起炎症,并通过插入突变引起癌症,但先天性和适应性免疫系统可以控制其中的大部分。我们发现Apobec 3酶以活性分级的方式减少小鼠边缘区B细胞的数量,但不减少滤泡B细胞或T细胞的数量。因此,我们认为内源性逆转录因子驱动边缘区B细胞群的发育和/或扩增。在本申请中,我们建议测试逆转录酶活性是否是边缘区B细胞固有的,并鉴定逆转录酶
英文摘要
DESCRIPTION (provided by applicant): The role of Apobec3 enzymes in regulation of marginal zone B cells The Apobec3 enzymes are intensely studied restriction factors of exogenous and endogenous retroelements (retroviruses and retrotransposons). Endogenous retroelements make up almost half of the mouse and human genomes-many of them somatically active. They often are interspersed within cellular genes and are thus transcribed along with cellular genes. Unrestricted retroelements can cause inflammation and, via insertional mutagenesis, cancer, but the innate and adaptive immune systems keep most of them in check. We found that Apobec3 enzymes decrease, in an activity-graded manner, the number of marginal zone B cells of mice, but not the number of follicular B cells or T cells. We, therefore, suggest that endogenous retroelements drive the development and/or expansion of the marginal zone B-cell population. In this grant application, we propose to test whether the retroelements activity is intrinsic to the marginal zone B cells, and to identify the retroelements
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