生物谷报道：来自美国国家健康局的科学家最近在NIAMS的资助下，发现在动物活体中追踪酶活动的方法，这种酶在正常免疫反应及自体免疫、B细胞肿瘤发育过程中都起着重要作用。结果发表在《Journal of Experimental Medicine》上。
这种酶被称为胞啶脱氨酶或AID，它由B细胞表达。B细胞产生于骨髓，负责产生用于攻击外来入侵者的抗体。AID酶能使细胞精确的对几乎所有入侵者做出反应，但它也有副作用。
文章第一作者，NIAMS的分子免疫学科学家Rafael Casellas表示，B细胞不断的扫描整个身体。当B细胞发现外来入侵者后，就会聚集到扁桃体、脾脏、淋巴结等处，然后大量分裂，并表达AID酶，这将造成细胞抗体蛋白基因的变异。大部分时候，这些变异是有利的，因为它使B淋巴细胞攻击入侵者。但是有时AID相关变异会造成不好的副作用，例如自体免疫，或者B细胞肿瘤等（Burkitt淋巴瘤）。
Casellas说：“了解AID在常规免疫反应及肿瘤化、自体免疫过程中如何被管理是非常重要的。”但最大的问题是，在此之前没有使AID酶在活体生物中可见的方法。
因此Casellas和他的同事制造了一种转基因老鼠，其中有一种来自水母的绿色荧光蛋白结合在AID上。在这些转基因老鼠中，B细胞在免疫反应中表达的是带有标记的酶。而在另一种转基因老鼠中，科学家使得来自扁桃体、脾脏、淋巴结的B细胞带有黄色荧光蛋白。因此科学家就可以进行追踪了。
英文原文链接：http://www.physorg.com/news98643282.html
原始出处：
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: casellar@mail.nih.gov
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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