Role of Teleost Fish B Cell Subsets in Innate and Adaptive Immunity Against Pathogens

B细胞负责脊椎动物免疫系统中抗体的产生。桑耶博士实验室最近的研究出人意料地发现，与哺乳动物的B细胞不同，多骨鱼类中的B细胞具有强大的吞噬和杀菌能力。他的实验室还发现了一种新的B细胞系，专门表达表面IGT免疫球蛋白。重要的是，IGT系统已被发现专门处理粘膜免疫反应。这一新项目的总体目标是使用两个互补的鲑鱼病原体模型(ruckeri耶尔森氏菌和沙斯塔甲藻)来测试IGT和IgM反应是否分别划分为粘膜和全身部位，并分析IGT+和IgM+B细胞亚群在感染过程中先天炎症反应发展中的特殊作用。虹鱼将感染这两种病原体，并在感染过程中测量先天和获得性免疫B细胞反应。这些反应将包括这些B细胞内化和杀死病原体的能力，以及它们产生一系列促炎和抗炎细胞因子的能力。预计IGT+B细胞将在黏膜反应中发挥重要作用，而IgM+B细胞将在全身反应中发挥关键作用。预计这两个B细胞亚群将在促炎和抗炎反应的发展中发挥重要作用。该项目将继续在该实验室对代表性不足的少数群体进行培训，并培训一名博士后研究员。在更广泛的层面上，这里提出的研究将造福社会，为水产养殖业做出贡献，因为更好地了解鱼类免疫系统对于开发新的治疗剂和疫苗以预防鱼类疾病至关重要。

B cells are responsible for antibody production in vertebrate immune systems. Recent studies in Dr. Sunyer's laboratory have produced the unexpected finding that unlike mammalian B cells, B cells in bony fish have potent phagocytic and bactericidal capacities. His lab has also found a novel B cell lineage expressing exclusively surface IgT immunoglobins. Importantly, the IgT system has been found to be specialized in mucosal immune responses. The overarching goal of this new project is to use two complementary trout-pathogen models (Yersinia ruckeri and Ceratomyxa shasta) to test whether IgT and IgM responses are compartmentalized into mucosal and systemic sites, respectively, and to analyze the specific contributions of IgT+ and IgM+ B cell subsets in the development of an innate inflammatory response during the course of infection. Rainbow trout will be infected with these two pathogens and innate and adaptive immune B cell responses will be measured during the course of infection. The responses will include the capacity of these B cells to internalize and kill the pathogens, and their ability to produce a range of pro-inflammatory and anti-inflammatory cytokines. It is expected that IgT+ B cells will play an important role in mucosal responses whereas IgM+ B cell will play a key role in systemic responses. It is expected that both B cell subsets will play a significant role in the development of pro- and anti-inflammatory responses. This project will continue the training of underrepresented minorities in this laboratory as well as the training of one postdoctoral fellow. On a broader level, the studies proposed here will benefit society by contributing to the aquaculture industry since better knowledge of the fish immune system is essential to develop new therapeutic agents and vaccines to prevent fish diseases.