Characterisation of the Mechanism of B Cell Receptor Triggering

免疫系统是人体抵御感染的机制。免疫系统由多层保护组成，其复杂性逐渐增加。(1)简单的屏障，如皮肤，防止有害物质进入体内。(2)先天免疫反应。这是一种“硬连线”反应，能够迅速作出反应，但以非常简单和刻板的方式作出反应。(3)适应性免疫反应。这是第二道防线，速度较慢，但更聪明。它专门针对个别威胁，并能够生成内存，以防止未来来自同一外国代理的感染。适应性免疫反应是由一组称为淋巴细胞的白色血细胞协调的。B细胞是淋巴细胞的一种形式，其在血液中循环并产生针对单个外来因子的特异性抗体。抗体与外来物质结合并将其作为破坏目标。当B细胞表面上的受体识别其靶标时，抗体产生响应于B细胞的活化而被刺激。然后产生对该特定靶点具有特异性的抗体。有些B细胞是持久的，并提供记忆，例如在接种疫苗后发生的记忆。外来物质与B细胞受体结合的过程激活B细胞并向其发出信号以产生抗体。支持B细胞活化的许多分子机制已经很好地建立。然而，目前尚不清楚的是，与靶点结合的受体实际上是如何激活这组信号的。在这个项目中，我们着手研究这种所谓的“触发”机制的B细胞。对这一科学领域的理解具有重大的潜在影响，因为当它出错时，它可能导致疾病。B细胞的不适当触发可能导致身体攻击无害目标的情况。这些目标可能包括正常的身体成分。这一过程类似于“友好火灾”，并导致自身免疫性疾病，如糖尿病，类风湿性关节炎和系统性红斑狼疮（SLE）。在匡威的情况下，当触发机制未能检测到外来因子时，威胁没有被根除，这可能导致感染恶化。为了确定在这些医疗条件下出了什么问题，我们首先需要建立正常的过程。这就是我们的研究试图理解的。我们将与我的导师Richard Cornall教授和Simon Davis教授合作，使用基于实验室的方法来确定这种触发机制如何在个体B细胞受体水平上发生。

The immune system is the body's mechanism of defence against infection. The immune system consists of multiple layers of protection of progressively increasing complexity. (1) Simple barriers such as the skin that prevent access of harmful agents into the body.(2) The "innate" immune response. This is a "hard-wired" response that is able to respond quickly but does so in a very simple and stereotyped manner.(3) The "adaptive" immune response. This is a second-line of defence which is slower but cleverer. It targets individual threats specifically and is capable of generating memory to prevent future infections from the same foreign agent. The adaptive immune response is orchestrated by a group of white blood cells known as lymphocytes. B cells are one form of lymphocyte that circulate in the blood and produce antibodies specific to individual foreign agents. Antibodies bind to foreign material and target them for destruction. Antibody production is stimulated in response to activation of B cells when the receptor on their cell surface recognises its target. Antibodies are then produced that are specific for that particular target. Some B cells are long lasting and provide memory such as occurs after vaccination.The process of foreign material binding to the B cell receptor activates the B cell and signals it to produce antibody. Many of the molecular mechanisms that underpin this activation of B cells are well established. However, what remains unclear is how the receptor binding to the target actually activates this set of signals. In this project we set out to investigate this so called "triggering" mechanism of B cells. An understanding of this area of science has significant potential implications since when it goes wrong it can lead to disease. An inappropriate triggering of B cells can lead to a situation in which the body attacks non-harmful targets. These targets could include normal body components. This process is analogous to "friendly-fire" and leads to autoimmune conditions such as diabetes, rheumatoid arthritis and systemic lupus erythromatosis (SLE). In the converse scenario when the triggering mechanism fails to detect a foreign agent a threat is not eradicated and this can lead to worsening infection. In order to ascertain what goes wrong in these medical conditions we first need to establish the normal process. This is what our research is attempting to understand. Working together with my supervisors, Professor Richard Cornall and Professor Simon Davis, we will use a laboratory-based approach to establish how this triggering mechanism happens at the level of individual B cell receptors.