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

记忆 B 细胞通过淋巴结被膜下窦迁移的作用

基本信息

批准号：
BB/S003800/1
负责人：
Kai-Michael Toellner
金额：
$ 73.7万
依托单位：
University of Birmingham
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2018
资助国家：
英国
起止时间：
2018 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FS003800%2F1
关键词：
Role memory cell migration through

项目摘要

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.

疫苗接种计划是全球公共卫生战略的核心要素，是预防各种危及生命的感染的关键。疫苗如何诱导对细菌和病毒的免疫记忆仍然知之甚少。我们知道，疫苗接种和感染会诱导B细胞发生突变，并使其编码抗体的基因适应疫苗上所见的结构。这些突变将导致产生高度特异性的抗体，可以中和细菌或病毒。在这个过程中也产生了长寿的记忆B细胞，它将这些突变保存了很长一段时间。我们最近观察到，记忆B细胞不仅在体内传播并保存了遇到的疫苗信息，它们似乎还收获了遇到的疫苗颗粒，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为什么记忆B细胞会进行这种抗原采集，以及哪些因素对其进行调节。为了了解这种调节，我们将产生不能产生一系列受体的B细胞，这些受体指导记忆B细胞迁移。为了了解抗原转运的功能，我们将破坏该过程并测试有效的B细胞成熟是否依赖于记忆B细胞的持续抗原收获和转运。老年人在有效产生对疫苗的良好抗体反应方面存在问题。在他们的B细胞成熟过程中看到的一些缺陷可能是由于记忆B细胞在抗原收集方面的缺陷，我们计划测试这一过程是否在老年免疫系统中被破坏。我们可以更好地了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反应可能会导致如何纠正这一过程的想法。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Role of B-cell receptors for B-cell development and antigen-induced differentiation.

DOI：
10.12688/f1000research.13567.1
发表时间：
2018
期刊：
F1000Research
影响因子：
0
作者：
Yam-Puc JC;Zhang L;Zhang Y;Toellner KM
通讯作者：
Toellner KM

Enhanced BCR signaling inflicts early plasmablast and germinal center B cell death.

DOI：
10.1016/j.isci.2021.102038
发表时间：
2021-02-19
期刊：
iScience
影响因子：
5.8
作者：
Yam-Puc JC;Zhang L;Maqueda-Alfaro RA;Garcia-Ibanez L;Zhang Y;Davies J;Senis YA;Snaith M;Toellner KM
通讯作者：
Toellner KM

Recycling of memory B cells between germinal center and lymph node subcapsular sinus supports affinity maturation to antigenic drift.