IEL B-cells: Phenotype and Developmental Requirements

描述（由申请人提供）：胃肠道（GI）的免疫稳态涉及超过100万亿细菌的隔室炎症的衰减。体内平衡涉及宿主和肠道细菌共生体表达的各种特性。这种平衡的丧失导致临床上重要的慢性粘膜炎症性疾病，但维持胃肠道稳态的具体因素仅部分了解。一个新兴的保护性群体是粘膜b细胞，基于口腔耐受、慢性呼吸道疾病和结肠炎的模型。在这个项目中，我描述了宿主-细菌界面上一个新发现的群体的功能表型和发育要求，肠上皮内淋巴细胞（IEL） b细胞。通过基因要求，我将阐明填充这个隔室的前体b细胞。通过肠道细菌和宿主基因操作，我将确定这个群体的形成/生存是如何由肠道细菌感应由TLR和B细胞抗原受体系统控制的。我的初步结果支持我的主要目标的可行性，以及IEL b细胞在粘膜免疫生理学中的新作用。

DESCRIPTION (provided by applicant): Immunologic homeostasis in the gastrointestinal (GI) tract involves the attenuation of inflammation in a compartment with more than 100 trillion bacteria. Homeostasis involves a variety of traits expressed by the host and the enteric bacterial commensals. The loss of this balance results in clinically important chronic mucosal inflammatory disorders, but the specific factors responsible for maintaining GI homeostasis are only partly understood. One emerging protective population is the mucosal B-cell, based on models of oral tolerance, chronic respiratory disease, and colitis. In this project, I characterize the functional phenotype and developmental requirements for a newly appreciated population at the host-bacterial interface, the intestinal intraepithelial lymphocyte (IEL) B-cell. Through genetic requirements, I will clarify the precursor B-cells filling this compartment. Through enteric bacterial and host genetic manipulations, I will determine how the formation/survival of this population is controlled by lumenal bacterial sensing by the TLR and B cell antigen receptor systems. My preliminary results support the feasibility of my key aims, and for a novel role of IEL B-cells in mucosal immune physiology.