Mechanisms of B cell responses to particulate antigens

B 细胞对颗粒抗原的反应机制

基本信息

批准号：
10437883
负责人：
Wei Cheng
金额：
$ 68.98万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10437883
关键词：
Address Affinity Animals Antibodies Antibody Response Antibody titer measurement Antigens Autoantigens B-Cell Activation B-Cell Antigen Receptor B-Lymphocytes Biophysics Cell Communication Cells DNA Dissection Encapsulated Ensure Epitopes Event Exposure to Generations Genetic Materials Goals Human Immune response Immunity Immunoglobulin Class Switching Immunoglobulin G In Vitro Individual Infection Invaded Investigation Knowledge Liposomes MHC Class II Genes Mediating Membrane Proteins Memory B-Lymphocyte Modeling Molecular Mus Nucleic Acids Particle Size Particulate Plasma Cells Proteins RNA Receptor Signaling Recovery Reporter Shapes Signal Pathway Signal Transduction Surface Surface Antigens System T-Lymphocyte Techniques Testing Time Titrations Toll-like receptors Transgenic Model Vaccine Design Vaccines Viral Viral Antigens Viral Genome Virion Virus Virus Diseases base chemical genetics density expectation functional outcomes in vivo innovation live cell imaging novel novel vaccines pandemic disease particle pathogen pathogenic virus programs rational design response single molecule success virus envelope

项目摘要

PROJECT SUMMARY Mechanisms of B cell responses to particulate antigens Two biophysical attributes shared by most animal viruses are the display of viral-specific proteins at certain densities on the surface of individual virions and the encapsulation of viral genome inside the virion. A threshold density of viral surface proteins is important to ensure efficient viral infection of host cells. From the perspective of the host, a threshold density of viral surface proteins may also be critical for the recognition by germline B cells for efficient mounting of humoral responses. The encapsulated genetic material may also stimulate B cells through the Toll-like receptors. Substantial mechanistic studies at the single-molecule level and imaging of live cells have revealed the sensitivity of B cells to the density of antigens. However, at the mechanistic level, it remains largely uncharacterized how B cells may recognize and respond to the individual as well as collective attributes of a virus, including the spatial density of proteins and the internal nucleic acids. This project aims to unravel the cellular and molecular mechanisms of B cell responses to viral features both in vivo and in vitro, using a new generation of model particulate antigens that we have recently developed. The success of this project will yield new and important mechanistic information on how B cells recognize particulate antigens similar to viruses, and reveal the functional outcomes of B cells in response to the recognition of the biophysical features of these antigens.

项目摘要 B细胞对颗粒抗原的反应机制大多数动物病毒共有的两个生物物理属性是在某些情况下显示病毒特异性蛋白单个病毒体表面的密度以及病毒基因组在病毒体内的封装。阈值病毒表面蛋白的密度对于确保有效的宿主细胞病毒感染很重要。从角度来看在宿主中，病毒表面蛋白的阈值密度对于种系B的识别也可能至关重要细胞有效地安装体液反应。封装的遗传物质也可能刺激B细胞通过类似收费的受体。单分子水平和现场成像的实质机械研究细胞揭示了B细胞对抗原密度的敏感性。但是，在机械级别上在很大程度上仍然没有表征B细胞如何识别和响应个人以及集体病毒的属性，包括蛋白质和内核酸的空间密度。这个项目旨在揭示B细胞对病毒特征的细胞和分子机制在体内和体外，使用我们最近开发的新一代模型颗粒抗原。这个成功项目将产生有关B细胞如何识别颗粒抗原相似的新的重要机械信息为病毒，并揭示B细胞的功能结果，以响应生物物理特征的识别这些抗原。