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禽类免疫球蛋白基因多样化的分子机制及其在工业应用方面的前景。

Molecular mechanisms of avian immunoglobulin gene diversification and prospect for industrial applications.

机构信息

Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.

Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Tokyo, Japan.

出版信息

Front Immunol. 2024 Sep 13;15:1453833. doi: 10.3389/fimmu.2024.1453833. eCollection 2024.

Abstract

Poultry immunoglobulin genes undergo diversification through homologous recombination (HR) and somatic hypermutation (SHM). Most animals share a similar system in immunoglobulin diversification, with the rare exception that human and murine immunoglobulin genes diversify through V(D)J recombination. Poultry possesses only one functional variable gene for each immunoglobulin heavy (HC) and light chains (LC), with clusters of non-productive pseudogenes upstream. During the B cell development, the functional variable gene is overwritten by sequences from the pseudo-variable genes via a process known as gene conversion (GC), a kind of HR. Point mutations caused in the functional variable gene also contribute to immunoglobulin diversification. This review discusses the latest findings on the molecular mechanisms of antibody gene diversification in poultry, using chickens as a model. Additionally, it will outline how these basic research findings have recently been applied especially in the medical field.

摘要

家禽的免疫球蛋白基因通过同源重组(HR)和体细胞高频突变(SHM)进行多样化。大多数动物在免疫球蛋白多样化方面具有相似的系统,只有人类和鼠类的免疫球蛋白基因通过 V(D)J 重组进行多样化是罕见的例外。家禽的每个免疫球蛋白重链(HC)和轻链(LC)只有一个功能性可变基因,上游有簇状非功能假基因。在 B 细胞发育过程中,功能性可变基因通过一种称为基因转换(GC)的 HR 过程,被来自伪基因的序列覆盖。功能性可变基因中的点突变也有助于免疫球蛋白多样化。本综述以鸡为模型,讨论了家禽抗体基因多样化的分子机制的最新发现,并概述了这些基础研究发现最近是如何特别在医学领域得到应用的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9789/11427246/623ea238c1d1/fimmu-15-1453833-g001.jpg

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