Cell-intrinsic roles of P110delta in primary and memory antibody responses

抗体的产生对免疫至关重要，也是疫苗接种刺激的关键过程之一。随着年龄的增长，疫苗失败变得更加常见，这在很大程度上是由于未能激发抗体。抗体是由称为浆细胞的特殊细胞分泌的，浆细胞是B淋巴细胞的后代，B淋巴细胞是白细胞的一种特殊(分化)形式。我们的研究旨在了解哺乳动物中B淋巴细胞分化过程是如何调节的。尽管付出了巨大的努力，但这不能通过在专门的培养基和孵化器中培养细胞来模仿。因此，我们必须使用动物模型；在这种情况下，我们使用小鼠，部分原因是我们有很多研究工具来详细研究B淋巴细胞分化，还因为我们已经知道了很多关于这个系统的知识，包括它与其他动物的相似之处。这使我们能够提出和研究复杂的问题。我们已经知道，当B淋巴细胞被抗原刺激时，它们可能会迅速分化为分泌抗体的浆细胞，这些浆细胞驻留在特定的解剖位置。或者，它们可能成为快速增殖但不分泌抗体的生发中心细胞。这两种不同的细胞命运都由称为T淋巴细胞的第二种类型的细胞来调节。我们的研究关注的是促进这些B细胞命运决定的T淋巴细胞的特征。为了激发免疫反应，小鼠将被模型抗原挑战，包括一种减毒(非致病)形式的沙门氏菌。对这些挑战的反应将被测量，以计数每种不同类型的细胞的数量，并确定它们的准确解剖位置。这一过程将被针对T细胞的细胞激活途径的特定突变所干扰；包括B淋巴细胞在内的所有其他细胞将保持正常，从而我们可以得出结论，B淋巴细胞表现出的任何行为变化都将是由于T细胞的缺陷造成的。

The production of antibodies is critical for immunity and is one of the key processes stimulated by vaccination. Vaccine failure, which becomes more common upon ageing, is largely due to a failure to elicit antibodies. Antibodies are secreted by specialised cells called plasma cells which are the descendents of the B-lymphocyte, a specialized (differentiated) form of white blood cell. Our study is aimed at understanding how the process of B lymphocyte differentiation is regulated in the mammal. Despite great effort, this cannot be mimicked by culturing cells in specialized media and incubators. Therefore we have to use animal models; in this case we use the mouse, partly because we have a great many research tools to study B lymphocyte differentiation in detail and also because we already know much about the system including how it is similar to other animals. This allows us to ask and examine sophisticated questions. We already know that when B lymphocytes are stimulated by antigen they may either quickly differentiate into antibody secreting plasma cells, which reside in a specific anatomical location. Alternatively they may become rapidly proliferating, but non-antibody secreting, germinal centre cells. Each of these two alternative cell fates is regulated by second type of cell called the T-lymphocyte. Our study is concerned with characterising the T-lymphocytes which promote each of these B cell fate decisions. To provoke an immune response, mice will be challenged with model antigens including an attenuated (not-virulent) form of salmonella. The responses to these challenges will be measured to count the numbers of each type of different cell and determine their precise anatomical location. The process will be perturbed by specifically targeting mutations of a cell activation pathway to the T cells; all other cells, including the B lymphocytes, will remain normal allowing us to conclude that any altered behaviour B lymphocytes display will be due to a defect in the T cells.