Mechanisms controlling antibody production by modulating B cell antigen receptor signalling

该项目将分析调节健康和疾病中抗体产生的机制。在健康方面，抗体通常是专门针对感染性病原体制造的，提供持久的免疫力。抗体产生控制中的未知错误会导致自身免疫性疾病，如系统性红斑狼疮或类风湿性关节炎，这些疾病是针对我们身体的部分产生抗体的，或者是导致过敏的，这些过敏是针对我们环境中的无害元素产生的。为了开发合理、特异的治疗这些疾病的方法，有必要识别和了解通常控制针对感染性病原体、自身成分和无害环境病原体的抗体形成的生化机制。该项目的重点是确定抗体形成细胞，即B淋巴细胞，感知感染性、无害或自身成分的生化机制。这些细胞携带特定的受体，结合这些成分并将信号传递到B淋巴细胞。这项研究将确定不同类型的信号是如何由受体传递的，因此，通常情况下，针对感染性病原体的抗体会大量产生，但针对自身成分的抗体很少。通过确定信号类型是如何改变的，该项目的结果将揭示在自身免疫、过敏或免疫缺陷中可能改变的控制机制，并可能被用作药物靶点，以防止不必要的抗体产生来治愈这些疾病。

This project will analyse mechanisms that regulate antibody production in health and disease. In health, antibodies are normally made exclusively against infectious agents, providing long-lasting immunity. Unknown errors in the control of antibody production result in autoimmune diseases such as systemic lupus or rheumatoid arthritis, where antibodies are made against parts of our own bodies, or result in allergies where antibodies are made against innocuous elements of our environment. In order to develop rational, specific methods for treating these diseases, it is necessary to identify and understand the biochemical mechanisms that normally control antibody formation against infectious agents, self components, and innocuous environmental agents. The project focuses on defining the biochemical mechanisms by which the antibody-forming cells, B lymphocytes, sense infectious, innocuous, or self components. These cells carry specific receptors that bind these components and transmit signals into the B lymphocyte. The research will determine how different types of signal are transmitted by the receptor so that, normally, large amounts of antibody are made against infectious agents but very little antibody is made against self components. By identifying how the types of signals are changed, the results of this project will reveal control mechanisms that may be altered in autoimmunity, allergy or immune deficiency, and that may be able to be used as drug targets to prevent unwanted antibody production to cure these diseases.