Role of memory B cell migration through the lymph node subcapsular sinus

疫苗接种方案是全世界公共卫生战略的核心内容，是预防各种危及生命的感染的关键。疫苗如何诱导细菌和病毒的免疫记忆仍然知之甚少。我们知道，疫苗接种和感染诱导B细胞突变并使其编码针对疫苗上所见结构的抗体的基因发生变化。然后，这些突变将导致产生高度特异的抗体，可以中和细菌或病毒。在这个过程中也产生了长寿命的记忆B细胞，这些细胞将这些突变保存很长一段时间。我们最近观察到，记忆B细胞不仅在体内传播并保存所遇到的疫苗的信息，而且它们似乎还收集了它们遇到的疫苗颗粒，并将它们运送回B细胞成熟的地方。这个项目的目的是了解记忆B细胞为什么会采集抗原，以及哪些因素调节它。为了理解这种调节，我们将生产不能产生一系列受体来指导记忆B细胞迁移的B细胞。为了了解抗原运输的功能，我们将扰乱这一过程，并测试有效的B细胞成熟是否依赖于记忆B细胞持续的抗原获取和运输。老年人在有效地产生对疫苗的良好抗体反应方面存在问题。在B细胞成熟过程中出现的一些缺陷可能是由于记忆B细胞获取抗原的缺陷，我们计划测试这一过程是否在衰老的免疫系统中被破坏。这个项目的结果将有助于更好地理解疫苗如何诱导保护性免疫反应和记忆。我们可能会更好地理解疫苗应该如何设计或交付。更好地理解为什么老年人对疫苗接种没有有效的反应，可能会导致关于如何纠正这一过程的想法。

Vaccination programmes are a core element of public health strategy worldwide and are key to preventing a wide range of life threatening infections. How vaccines induce immune memory to bacteria and viruses are still poorly understood. We know that vaccination and infection induces B cells to mutate and adapt their genes coding for antibody specific to structures seen on the vaccine. These mutations then will lead to the production of highly specific antibody that can neutralize bacteria or viruses. During this process are also long-lived memory B cells generated, which preserve these mutations for a long time.We recently observed that memory B cells not only spread through the body and preserve information on vaccines encountered, they also seem to harvest vaccine particles they encounter and transport them back to the places where B cells mature. The purpose of this project is to understand why memory B cells do this antigen harvest, and which factors regulate it. To understand the regulation, we will produce B cells that cannot produce a range of receptors that direct memory B cell migration. To understand the function of antigen transport, we will disrupt the process and test whether efficient B cell maturation is dependent on continued antigen harvest and transport by memory B cells. Aged people have problems efficiently producing good antibody responses to vaccines. Some of the defects seen during their B cell maturation may be due to a defect in antigen harvest by memory B cells, and we plan to test whether this process is disrupted in the aged immune system.Results from this project will help to better understand how vaccines induce protective immune responses and memory. We may better understand how vaccines should be designed or delivered. Better understanding why elderly do not react efficiently to vaccination may lead to ideas on how to correct this process.