Mechanisms of B cell responses to particulate antigens

B 细胞对颗粒抗原的反应机制

• 批准号: 10296438
• 负责人: Wei Cheng
• 金额: $ 70.38万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 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/10296438
• 关键词: Address; Affinity; Animals; Antibodies; Antibody Response; Antibody titer measurement; Antigens; Antiviral Agents; 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; design; expectation; functional outcomes; in vivo; innovation; live cell imaging; novel; novel vaccines; pandemic disease; particle; pathogen; pathogenic virus; programs; response; single molecule; success; virus envelope

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.

项目总结 B细胞对颗粒抗原的应答机制 大多数动物病毒共有的两个生物物理属性是在一定程度上显示病毒特有的蛋白质 单个病毒粒子表面的密度和病毒基因组在病毒粒子内的包裹情况。一个门槛 病毒表面蛋白的密度是确保病毒有效感染宿主细胞的重要因素。从这个角度来看 在宿主中，病毒表面蛋白的阈值密度对于生殖系B的识别也可能是关键的 用于有效安装体液反应的细胞。被包裹的遗传物质也可能刺激B细胞 通过Toll样受体。单分子水平的实质性机制研究和活体成像 细胞揭示了B细胞对抗原密度的敏感性。然而，在机制层面上，它 B细胞如何识别和响应个体和集体在很大程度上仍未确定 病毒的属性，包括蛋白质和内部核酸的空间密度。该项目旨在 解开体内和体外B细胞对病毒特性反应的细胞和分子机制， 使用我们最近开发的新一代模型颗粒抗原。这件事的成功 该项目将产生关于B细胞如何识别类似颗粒抗原的新的重要机制信息 对病毒的作用，并揭示B细胞对生物物理特征的识别的功能结果 这些抗原中的一种。