Characterisation of the Mechanism of B Cell Receptor Triggering

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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.