Genetic analysis of the role of the PI3K signalling in humoral immunity

B淋巴细胞在暴露于抗原后分化为浆细胞时会产生抗体。抗体是免疫的关键媒介，是保护我们免受细菌、真菌和病毒等病原微生物侵袭所必需的。产生强有力的抗体是免疫和疫苗接种原则的核心，几十年来人们都知道，在感染过程中，产生的抗体的质量会增加。揭示这种情况发生的机制可能会提供有助于疫苗设计的信息。对B淋巴细胞在健康和疾病中的研究与我们改进疫苗设计、开发自身免疫性疾病的新疗法以及开发对抗B细胞恶性肿瘤的疗法的努力直接相关。这个项目试图揭示当B细胞被激活时控制其发育和功能的基本机制。这项研究将使用遗传模型，在这些模型中，我们认为对抗体产生至关重要的单个基因的功能被特别关闭。这可以在特定的细胞类型或免疫反应的特定阶段实现。通过在特定细胞或特定时间删除候选基因，并测试对B细胞分化的影响以及产生和维持抗体产生的能力，我们将获得这些基因功能的良好证据。

Antibodies are produced by B lymphocytes when they differentiate into plasma cells following exposure to antigen. Antibodies are proteins that are key mediators of immunity required to protect us from pathogenic micro-organisms such as bacteria, fungi and viruses. The production of potent antibodies is central to immunity and the principle of vaccination and it has been known for many decades that during the course of an infection the quality of antibodies produced increases. Revealing the mechanism by which this takes place may provide information which will aid in vaccine design. The study of B lymphocytes in health and disease is directly relevant to our attempts to improve vaccine design; to develop new treatments for autoimmune disease; and to develop therapies to combat B cell malignancies. This project seeks to uncover the basic mechanisms that control the development and function of B cells when they are activated. The research will use genetic models in which the function of individual genes that we propose to be vital for antibody production is specifically switched off. This can be achieved in a specific cell type or at a particular stage of the immune response. By deleting candidate genes in specific cells or at specific times and testing the consequences for B cell differentiation and the ability to produce and sustain antibody production we will obtain good evidence for the function of the genes.