Mechanisms controlling antibody production by modulating B cell antigen receptor signalling

该项目将分析在健康和疾病中调节抗体产生的机制。在健康方面，抗体通常是专门针对传染性病原体产生的，提供持久的免疫力。控制抗体产生的未知错误导致自身免疫性疾病，如系统性狼疮或类风湿关节炎，在这些疾病中，抗体是针对我们自己身体的某些部分产生的，或者导致过敏，抗体是针对我们环境中的无害元素产生的，或者导致淋巴瘤、白血病和骨髓瘤中不受控制的B细胞积累。为了开发合理的、具体的治疗这些疾病的方法，有必要确定和了解通常控制针对感染因子、自身成分和无害环境因子的抗体形成的生化机制。该项目侧重于确定抗体形成细胞B淋巴细胞感知感染性、无害性或自身成分的生化机制。这些细胞携带特异性受体，结合这些成分并将信号传递给B淋巴细胞。这项研究将确定不同类型的信号是如何通过受体传递的，因此，通常情况下，大量的抗体是针对感染因子的，而很少的抗体是针对自身成分的，并且B细胞的积累受到严格限制。通过确定信号类型是如何改变的，本项目的结果将揭示在自身免疫、过敏、免疫缺陷或淋巴瘤中可能改变的控制机制，并可能用作治疗这些疾病的药物靶点。

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, or result in uncontrolled B cell accumulation in lymphoma, leukemia and myeloma. 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, and that B cell accumulation is tightly limited. 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, immune deficiency, or lymphoma, and that may be able to be used as drug targets to cure these diseases.