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

B细胞在脊椎动物的免疫系统中负责产生抗体。Sunyer博士的实验室最近的研究产生了一个意想不到的发现：与哺乳动物的B细胞不同，硬骨鱼的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只表达表面IgT免疫球蛋白的新型B细胞谱系。重要的是，已经发现IgT系统专门参与粘膜免疫反应。这个新项目的总体目标是使用两个互补的鳟鱼病原体模型（ruckeri Yersinia和Ceratomyxa shasta）来测试IgT和IgM反应是否分别被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的发展中的具体贡献。虹鳟鱼将感染这两种病原体，并在感染过程中测量先天和适应性免疫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细胞将在粘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培养代表性不足的少数民族，并培养一名博士后。在更广泛的层面上，这里提出的研究将通过为水产养殖业做出贡献而造福社会，因为更好地了解鱼类免疫系统对于开发新的治疗药物和预防鱼类疾病的疫苗至关重要。

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.