AID biology

援助生物学

• 批准号: 7138038
• 负责人: rafael c casellas
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7138038
• 关键词: B lymphocyte; autoimmunity; fluorescent dye /probe; gene mutation; genetically modified animals; green fluorescent proteins; histology; immunologic memory; laboratory mouse; leukocyte activation /transformation; microorganism immunology; monoclonal antibody; transfection

B lymphocytes are the immune system cells that recognize and dispose pathogens such as viruses and bacteria though special receptors on their cell surface known as antibodies. Both pathogen recognition and disposal are facilitated by two processes known as hypermutation and switching, which are carried out by a novel protein: AID. This year we have created three genetically modified mice to study the expression of this exciting molecule. 1- By fusing to the AID gene fluorescent molecules (such as the green fluorescent protein (GFP) isolated from the jellyfish Aequorea victoria), we are able to visualize B cells (green fluorescent cells) activated during infection or immunization. 2- We have introduced the human version of AID in mice by means of a transgene. Human AID can be visualized by histology with a very specific monoclonal antibody. This technique is allowing us to pinpoint the migration of activated B cells from their first encounter with antigen (or pathogen) until they become fully differentiated (memory or plasma cells) where AID is turned off. 3- To follow the progeny of cells that have expressed AID during development but subsequently turned its expression off, we have devised a method that permanently tags activated B cells with the yellow fluorescent molecule (a GFP variant). This tools permits the study of the memory response. Memory B cells, in contrast to naive ones, become rapidly activated upon interaction with previously encountered viruses or bacteria, and explain why we do not succumb to the same infection twice.

B淋巴细胞是一种免疫系统细胞，通过其细胞表面称为抗体的特殊受体识别和处置病原体，如病毒和细菌。病原体的识别和处理都通过两个称为超突变和转换的过程来促进，这两个过程是由一种新的蛋白质：AID实现的。今年，我们创造了三只转基因小鼠来研究这种令人兴奋的分子的表达。 1-通过与AID基因荧光分子(例如从水母Aequorea Victoria分离的绿色荧光蛋白(GFP))融合，我们能够可视化在感染或免疫期间激活的B细胞(绿色荧光细胞)。 2-我们已经通过转基因在小鼠身上引入了人类版本的艾滋病。用一种非常特异的单抗可以通过组织学观察到人类艾滋病。这项技术使我们能够精确定位激活的B细胞从第一次遇到抗原(或病原体)到它们完全分化(记忆或浆细胞)的迁移过程，在AID关闭的情况下。 3-为了跟踪在发育过程中表达AID但随后关闭其表达的细胞的后代，我们设计了一种方法，用黄色荧光分子(GFP变体)永久标记激活的B细胞。该工具允许研究记忆响应。与幼稚的B细胞不同，记忆B细胞在与以前遇到的病毒或细菌相互作用后迅速激活，并解释了为什么我们不会两次死于相同的感染。