重组激活基因(RAGs)功能机制及其在鱼类早期发育中的作用

Functional mechanisms of RAGs and its research progress in fish development

在B淋巴细胞和T淋巴细胞的发育过程中,BCR和TCR基因座(Igκ、Igλ、Igh、Tcrα、Tcrβ、Tcrγ、Tcrδ)的可变区(V)、多样区(D)、链接区(J)发生V(D)J重排,该重排过程是在重组激活蛋白(RAG-1和RAG-2)的作用下完成的,V(D)J重排机制使机体拥有庞大的抗体库,以应对自然界中多元的病原微生物。RAGs结构分为核心区和非核心区,核心区域发挥着重要的基因片段酶切功能,而非核心区域的九聚体序列(nonamer)、锌指等结构具有调节V(D)J重排的功能。RAGs的功能在转录水平、染色体水平以及蛋白水平受到严格的时间和空间调控,以保证B/T细胞的正常发育。随着国内外学者对哺乳动物RAGs基因的结构与功能机制的深入研究,RAGs也在淡水鱼和海水鱼中有了越来越多的报道。由于RAGs的功能特点以及在进化过程中的稳定性,其已成为研究鱼类免疫系统发育过程和系统进化的重要分子标记。本文在赤点石斑鱼(Epinephelus akaara)RAGs研究的基础上探讨了RAGs定位鱼类免疫系统的发生过程,旨在为鱼类人工繁殖技术的突破、鱼类疫苗的开发与研制以及鱼类免疫学研究等提供理论借鉴。

In the development process of B and T lymphocytes, variable region （V）, the diversity region （J） and joining region （D） of BCR and TCR loci （lgx, Ig2, Igh, Tcra, Tcrfl, Tcry and Tcrδ） are target of V（D）J recombination, which is completed under the recombination activating protein （RAG- 1 and RAG-2）. This rearrangement mechanism endows the body with a huge library of antibodies to resist the multiple pathogenic microorganisms in nature. RAGs structure is divided into a core and a non-core area, while the core area exerts an enzyme cutting function, and the non-core region, such as nonamer and zinc finger, plays a regulation role in V（D）J recombination. The expression of RAGs is regulated at the gene and protein levels with stringent temporal and spatial condition, in order to ensure the normal development of B/T cells. More and more reports of RAGs structure and function are found in freshwater and marine fish. According to the characteristics of RAGs and the stability in the evolution process, RAGs have been considered as wonderful in- dictors to research on fish immune system and system evolution. Based on the study of red-spotted grouper immune system, the development process of the immune system were discussed when RAGs were used as a marker, which would provide the basis for artificial propagation and fish vaccine.