CHECKPOINT FOR B CELL SURVIVAL IN HUMAN GUT

B细胞是免疫系统的细胞。B细胞通过B细胞表面非常特殊的受体（称为B细胞受体）识别感染性颗粒来对抗感染。B细胞受体通过它们的个体形状识别感染因子，并以锁与钥匙的方式与它们结合。数以百万计的B细胞在血液和身体组织中循环，每个B细胞都有一个独特的B细胞受体。因此，无论哪种感染因子进入人体，都会有一个具有互补形状受体的B细胞将其结合。如果一个B细胞通过它的B细胞受体与感染粒子结合，B细胞可能被激活并分泌它的B细胞受体，B细胞受体将与感染因子结合并对抗感染因子。当B细胞受体被分泌时，它被称为抗体。产生具有独特受体的大量多样的B细胞的过程有一个主要的相关危险。B细胞可以与人体自身的细胞和组织结合并攻击它们。免疫系统中的另一种叫做T细胞的细胞有能力调节B细胞，它们自己可以很好地区分自我和非自我。然而，许多B细胞可以产生与T细胞无关的反应，如果没有适当的特异性调节，这些反应是特别危险的。以不依赖t细胞的方式激活B细胞的感染因子包括那些引起某些类型肺炎的感染因子。B细胞有一个额外的技巧来识别这些药物，因为它们在表面上有一个重复的形状模式。B细胞可以通过B细胞受体识别形状，也可以识别形状呈现的规律性。我们实验室的实验表明，在肠道中发生的B细胞选择会阻止自身反应，并促进对独立于T细胞的激活B细胞的颗粒的反应。肠道中有很多“友好”细菌，它们会不断刺激肠道内的免疫系统。我们的实验表明，这种环境支持在人类B细胞免疫学模型或人类疾病评估中很大程度上被忽视的B细胞发育阶段。我们称其为“检查点”，因为这是B细胞发育的一个阶段，只有具有所需属性的细胞才被允许通过。在许多物种中，肠道以不同的方式参与了B细胞的发育，包括鸡、老鼠、羊和兔子。因此，肠道对人类B细胞发育的影响是重要的，而且极有可能发生，但迄今为止完全是神秘的。本应用程序中描述的实验目的是了解B细胞如何在肠道中成熟以及如何调节。

B cells are cells of the immune system. B cells fight infections by identifying infectious particles via very specific receptors on the B cell surface, called the B cell receptors. B cell receptors recognise infectious agents by their individual shape and they bind to them in a lock-and-key way. Millions of B cells circulate through the blood and tissues of the body and each B cell has a B cell receptor that is unique to that B cell. As a consequence, no matter what infectious agent finds its way into the body, there will be a B cell with a receptor of the complementary shape to bind it. If a B cell binds to an infectious particle via its B cell receptor, the B cell may become activated and secrete its B cell receptor that will bind to and fight the infectious agent. When the B cell receptor is secreted it is referred to as antibody.The process that generates the huge and diverse set of B cells with unique receptors has a major associated hazard. B cells can be produced that bind to the body's own cells and tissues and can attack them. Other cells of the immune system called T cells have the capacity to regulate B cells and they themselves can discriminate well between self and non-self. However, many B cells can make T cell independent responses and these are particularly dangerous if not properly regulated for specificity.The infectious agents that activate B cells in a T-cell independent way include those that cause some types of pneumonia. B cells have an additional trick to recognise these agents because they have a repeating pattern of shapes on the surface. B cells may be able to recognise the shape through the B cell receptor, but also the regularity with which the shape is presented. Experiments in our lab suggest that B cell selection that would prevent self-reactivity and promote responsiveness to particles that activate B cells independent of T cells happens in the gut. The gut contains a lot of 'friendly' bacteria that constantly stimulate the immune system it contains. Our experiments suggest that this environment supports stages in B cell development that are largely ignored in models of human B cell immunology or assessment of human disease. We call this a 'checkpoint' because it is a stage of B cell development where only cells that have a required set of properties are allowed to pass. The gut is involved in the development of B cells in different ways in many species, including chickens, mice, sheep and rabbits. Therefore an influence of the gut on human B cell development is important and highly likely to occur, but as yet totally mysterious.The aims of experiments described in this application are to understand how B cells mature in the gut and how this is regulated.