The role of Apobec3 enzymes in regulation of marginal zone B cells

描述(申请人提供)：APOBEC3酶在边缘带B细胞调节中的作用APOBEC3酶是对外源和内源逆转录因子(逆转录病毒和反转录转座子)的限制因素的深入研究。内源性逆转录因子几乎占到了老鼠和人类基因组的一半--其中许多在身体上是活跃的。它们通常散布在细胞基因中，因此与细胞基因一起转录。不受限制的逆转录元件可以引起炎症，并通过插入突变导致癌症，但先天和获得性免疫系统可以控制大多数逆转录酶。我们发现，APOBEC3酶以一种活性分级的方式减少小鼠边缘带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带B细胞群体的发展和/或扩张。在这项拨款申请中，我们建议测试逆转录元件的活性是否是边缘带B细胞所固有的，并鉴定逆转录元件

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