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.<br/><br/><br/>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.