The role of Semaphorin 4C-PlexinB2 interaction in B-lymphocyte differentiation

B淋巴细胞是制造抗体的细胞，为T细胞提供帮助，帮助放大对微生物和其他外来入侵者的免疫反应，并产生一种称为细胞因子的化学物质，将信息从一个细胞传递到另一个细胞。为了提高B淋巴细胞的交流能力，当B细胞被激活时，B细胞上的重要分子被带到细胞一侧的极点，这种结构被称为免疫突触。控制这些突触形成的分子还没有得到很好的研究。了解免疫突触的调节对于了解细胞如何交流并潜在地改善自身免疫和抗体缺陷等问题是重要的。我的实验室发现，一种被称为Semaphorin 4C的分子，被认为只在神经系统中重要，当B细胞被激活以成熟或对特定类型的外来蛋白质做出反应时，就会产生这种分子。这种分子在B细胞中的全部功能尚不清楚。然而，我们的数据表明，Semaphorin 4C是锚的一部分，允许B细胞正确地形成免疫突触。在没有这种分子的小鼠中，被激活的B细胞不会形成正常的免疫突触，它们的B细胞也不会产生正常数量的抗体或细胞因子。已知信号素4C与F-肌动蛋白等分子相互作用，这些分子共同作用使细胞改变形状，就像拉提线木偶上的绳子一样。这个项目将研究Semaphorin 4C如何在细胞骨架内相互作用，以帮助形成免疫突触，并确定当免疫突触形成不良时，B细胞内信号的后果。了解这种锚分子的作用将有助于了解形成抗体的细胞生物学的基本方面，并有可能帮助我们更好地了解免疫缺陷、过敏和自身免疫状况等疾病。

B-lymphocytes are the cells that make antibodies, provide assistance to T-cells to help magnify immune responses against microbes and other foreign invaders, and produce chemicals called cytokines which transfer information from one cell to another. To improve the ability of B-lymphocytes to communicate, when B-cells are activated, important molecules on B-cells are brought to a pole on one side of the cell, in a structure known as the immune synapse. The molecules that control the formation of these synapses are not well studied. It is important to understand the regulation of the immune synapse to understand how cells communicate and potentially improve problems such as autoimmunity and antibody deficiencies. My laboratory discovered that a molecule known as Semaphorin 4C, thought to be only important in the nervous system, is produced when B-cells are activated to mature or to respond to particular types of foreign proteins. The full function of this molecule in B-cells is not known. However, our data suggests that Semaphorin 4C acts a part of the anchor allowing B-cells to properly form immune synapses. In mice that do not have this molecule, B-cells which are activated do not form normal immune synapses and their B-cells do not make normal amounts of antibodies or cytokines. ******Semaphorin 4C is known to interact with molecules such as F-actin, that work together to allow a cell to change shape, much like pulling the strings on a marionette. This project will examine how Semaphorin 4C interacts within the cell skeleton to assist in forming an immune synapse, and determine the consequences of the signals within B-cells when the immune synapse is poorly formed. Understanding the role of this anchor molecule will help to understand fundamental aspects of the biology of the cells that form antibodies, and help us potentially better understand diseases such as immune deficiencies, allergies and autoimmune conditions.