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层组成，这些保护层的复杂性逐渐增加。(1)防止有害物质进入人体的简单屏障，如皮肤。(2)“先天”免疫反应。这是一种“硬连线”反应，能够快速反应，但以一种非常简单和刻板的方式进行。(3)“适应性”免疫反应。这是第二道防线，速度更慢，但更聪明。它专门针对单个威胁，并能够生成记忆，以防止未来来自同一外来病毒的感染。适应性免疫反应是由一群被称为淋巴细胞的白血球协调的。B细胞是淋巴细胞的一种形式，它在血液中循环，并产生针对个别外来病原体的抗体。抗体与外来物质结合，并以此为目标进行破坏。当B细胞表面的受体识别其目标时，抗体的产生是对B细胞激活的反应。然后产生针对该特定靶点的抗体。有些B细胞持续很长时间，并提供记忆，就像接种疫苗后发生的那样。异物与B细胞受体结合的过程激活B细胞，并向其发出产生抗体的信号。支持B细胞这种激活的许多分子机制已经得到了很好的证实。然而，仍然不清楚的是，与靶标结合的受体实际上是如何激活这一组信号的。在这个项目中，我们着手研究这种所谓的B细胞的“触发”机制。对这一科学领域的理解具有重大的潜在意义，因为当它出错时，可能会导致疾病。不适当地触发B细胞可能会导致身体攻击无害目标的情况。这些靶点可能包括正常的身体成分。这一过程类似于“友军之火”，会导致自身免疫疾病，如糖尿病、类风湿性关节炎和系统性红斑狼疮(SLE)。在相反的情况下，当触发机制未能检测到外来因素时，威胁不会被根除，这可能会导致感染恶化。为了确定在这些医疗条件下哪里出了问题，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。与我的导师Richard Cornall教授和Simon Davis教授合作，我们将使用基于实验室的方法来确定这种触发机制是如何在单个B细胞受体的水平上发生的。

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.