B Cell Development and Activation in Zebrafish

斑马鱼是一种很有前途的脊椎动物模型，用于研究免疫和疾病的基本过程。 重要的是，斑马鱼拥有与哺乳动物相似的血细胞，因此使用斑马鱼的基础研究可以揭示对人类健康具有潜在意义的免疫和疾病的见解，这是这项研究的更广泛的科学影响。本项目的首要目标是研究斑马鱼B细胞的发育和激活。 B细胞是一种白色血细胞，可以产生抗体来保护脊椎动物免受入侵病原体的侵害。 虽然哺乳动物有四种类型的抗体产生B细胞，但鱼类只有两种类型：在哺乳动物中观察到的产生IgM的细胞，以及产生IgZ的细胞，这与哺乳动物抗体非常不同。因此，该项目的具体目标是分析IgM+和IgZ+ B细胞在斑马鱼中何时何地发育，以及这些B细胞如何保护鱼类免受各种病原体的侵害。这些研究的结果将直接应用于鱼类健康和水产养殖以及人类疾病的鱼类模型，将利用遗传方法创造转基因鱼，其中不同类型的B细胞用荧光蛋白标记。 先进的成像技术将用于跟踪B细胞的发育和激活。 预期IgM+和IgZ+ B细胞将根据鱼的年龄或它们所暴露的病原体的类型以不同的方式表现。这些实验的结果将增加我们对鱼类免疫系统的了解，并将揭示理解免疫系统进化所需的基本信息。 此外，将在本项目中开发的重要工具，表达荧光B细胞的转基因斑马鱼，将分发给斑马鱼社区，用于各种水产养殖和人类疾病模型。这一工具将促进和促进使用斑马鱼的其他研究，这是一个重要的预期成果。 另一个重要的更广泛的影响是为至少14名学生提供本科研究经验，包括代表性不足的学生。参与研究导致对科学如何进行的第一手了解，并已被证明可以增加学生的保留，然后在生物科学中进行研究生学习。

The zebrafish is a promising vertebrate model for the examination of basic processes in immunity and disease. Importantly, zebrafish possess blood cells similar to those of mammals, so that basic research using zebrafish can reveal insights about immunity and disease that have potential significance to human health, a broader scientific impact of this study. The overarching goal of this project is to examine B cell development and activation in zebrafish. B cells are white blood cells that produce antibodies to protect vertebrates from invading pathogens. Although mammals have four types of antibody-producing B cells, fish have just two types: those that produce IgM, which is observed in mammals, and those that produce IgZ, which is very different from mammalian antibodies. The specific goals of this project are thus to analyze when and where IgM+ and IgZ+ B cells develop in zebrafish and how these B cells protect fish from various pathogens. Results from these studies will have direct applications to fish health and aquaculture and to fish models of human diseases.Genetic approaches will be used to create transgenic fish in which the different types of B cells are marked with fluorescent proteins. Advanced imaging techniques will be used to track the development and activation of the B cells. It is expected that the IgM+ and IgZ+ B cells will behave in distinct ways depending upon the age of the fish or the type of pathogen to which they are exposed. Results from these experiments will increase our knowledge of the fish immune system and will reveal basic information needed to understand the evolution of immune systems. Moreover, the important tool that will be developed in this project, transgenic zebrafish expressing fluorescent B cells, will be distributed to the zebrafish community for use in a wide variety of aquaculture and human disease models. This tool will enable and catalyze additional research using zebrafish, a significant expected outcome. Another important broader impact is to provide undergraduate research experiences for at least 14 students, including underrepresented students. Participation in research leads to a first-hand understanding of how science is conducted, and has been shown to increase the retention of students who then pursue graduate studies in the biological sciences.