生物谷報道：來自美國國家健康局的科學(xué)家最近在NIAMS的資助下,，發(fā)現(xiàn)在動物活體中追蹤酶活動的方法，這種酶在正常免疫反應(yīng)及自體免疫,、B細(xì)胞腫瘤發(fā)育過程中都起著重要作用,。結(jié)果發(fā)表在《Journal of Experimental Medicine》上,。
這種酶被稱為胞啶脫氨酶或AID,，它由B細(xì)胞表達(dá)。B細(xì)胞產(chǎn)生于骨髓,，負(fù)責(zé)產(chǎn)生用于攻擊外來入侵者的抗體,。AID酶能使細(xì)胞精確的對幾乎所有入侵者做出反應(yīng)，但它也有副作用,。
文章第一作者,，NIAMS的分子免疫學(xué)科學(xué)家Rafael Casellas表示，B細(xì)胞不斷的掃描整個身體,。當(dāng)B細(xì)胞發(fā)現(xiàn)外來入侵者后,，就會聚集到扁桃體、脾臟,、淋巴結(jié)等處,，然后大量分裂,，并表達(dá)AID酶,，這將造成細(xì)胞抗體蛋白基因的變異。大部分時候,，這些變異是有利的,，因為它使B淋巴細(xì)胞攻擊入侵者。但是有時AID相關(guān)變異會造成不好的副作用,，例如自體免疫,，或者B細(xì)胞腫瘤等（Burkitt淋巴瘤）。
Casellas說：“了解AID在常規(guī)免疫反應(yīng)及腫瘤化,、自體免疫過程中如何被管理是非常重要的,。”但最大的問題是，在此之前沒有使AID酶在活體生物中可見的方法。
因此Casellas和他的同事制造了一種轉(zhuǎn)基因老鼠,，其中有一種來自水母的綠色熒光蛋白結(jié)合在AID上,。在這些轉(zhuǎn)基因老鼠中，B細(xì)胞在免疫反應(yīng)中表達(dá)的是帶有標(biāo)記的酶,。而在另一種轉(zhuǎn)基因老鼠中,，科學(xué)家使得來自扁桃體、脾臟,、淋巴結(jié)的B細(xì)胞帶有黃色熒光蛋白,。因此科學(xué)家就可以進(jìn)行追蹤了。
英文原文鏈接：http://www.physorg.com/news98643282.html
原始出處：
The Journal of Experimental Medicine, Vol. 204, No. 5, 1145-1156
Regulation of AID expression in the immune response
Elizabeth E. Crouch1, Zhiyu Li1, Makiko Takizawa1, Stefan Fichtner-Feigl2, Polyxeni Gourzi4, Carolina Montaño1, Lionel Feigenbaum5, Patrick Wilson6, Siegfried Janz3, F. Nina Papavasiliou4, and Rafael Casellas1
1 Genomic Integrity and Immunity, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 2 Mucosal Immunity Section, National Institute of Allergy and Infectious Diseases (NIAID), and 3 Laboratory of Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892
4 Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY 10021
5 Laboratory Animal Science Program, Science Applications International Corporation (SAIC), NCI, NIH, Frederick, MD 21702
6 Molecular Immunogenetics, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104
CORRESPONDENCE R. Casellas: [email protected]
Abstract
The B cell–specific enzyme activation-induced cytidine deaminase (AID) has been shown to be essential for isotype switching and affinity maturation of antibody genes during the immune response. Conversely, AID activity has also been linked to autoimmunity and tumorigenesis. Determining how AID expression is regulated in vivo is therefore central to understanding its role in health and disease. Here we use phylogenetic footprinting and high-resolution histone acetylation mapping to accurately demarcate AID gene regulatory boundaries. Based on this strategy, we identify a novel, positive regulatory element required for AID transcription. Furthermore, we generate two AID indicator mouse strains using bacterial artificial chromosomes that faithfully recapitulate endogenous AID expression. The first strain uses a green fluorescent protein reporter to identify B cells that actively express AID during the immune response. In the second strain, AID transcription affects the permanent expression of a yellow fluorescent protein reporter in post–germinal center and terminally differentiated lymphocytes. We demonstrate the usefulness of these novel strains by resolving recent contradictory observations on AID expression during B cell ontogeny.
Abbreviations used: Ab-MLV, Abelson murine leukemia virus; AID, activation-induced cytidine deaminase; BAC, bacterial artificial chromosome; CNS, conserved noncoding sequence; GC, germinal center; ILF, isolated lymphoid follicle; NP, nitrophenol; PP, Peyer's patch; QM, quasimonoclonal; SC-RT-PCR, single cell RT-PCR strategy; YFP, yellow fluorescent protein.
E.E. Crouch and Z. Li contributed equally to this work
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