Protective functions of influenza-specific lung-resident memory B cells

流感特异性肺驻留记忆 B 细胞的保护功能

基本信息

批准号：
10194374
负责人：
Troy D Randall
金额：
$ 70.53万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-16 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10194374
关键词：
Affinity Anti-Inflammatory Agents Antibodies Antigens Antiinflammatory Effect B Cell Proliferation B-Lymphocytes CD4 Positive T Lymphocytes Cell Differentiation process Cells Effector Cell Future Generations Helper-Inducer T-Lymphocyte Immunoglobulin Class Switching Impairment Individual Infection Infection prevention Inflammation Inflammatory Influenza Interferons Interleukin-10 Interleukin-6 Ligands Longevity Lung Lymphoid Tissue Maintenance Mediating Memory B-Lymphocyte Peripheral Phenotype Population Production Property Proteins Pulmonary Inflammation Respiratory System Site Specificity T-Lymphocyte TNFSF4 gene TNFSF5 gene Tissues Tumor Necrosis Factor-Beta Vaccinated Vaccines Virus Work antiviral immunity combat cytokine experimental study flu influenza infection influenza virus strain lymphoid organ mutant neutralizing antibody novel pathogen progenitor protective effect pulmonary vaccination repaired response self-renewal vaccination strategy

项目摘要

PROJECT SUMMARY We recently identified a novel population of flu-specific, lung-resident memory B cells (BRM cells) that are phenotypically different than systemic memory B cells, reside in unique sites in the lung and respond more rapidly to challenge infection than their systemic counterparts. Interestingly, lung BRM cells provide a significant degree of protection to challenge infection, even when they do not cross-react with the HA and NA proteins of the challenge virus, suggesting that BRM cells have additional effector functions beyond antibody (Ab) production. In fact, B cells make inflammatory cytokines like IFN, lymphotoxin, OX40L and IL-6, as well as anti-inflammatory cytokines like IL-10, IL-27 and IL-35. Moreover they are potent APCs, particularly for their cognate antigens. Thus, BRM cells have a variety of mechanisms, in addition to Ab, to modulate inflammation and promote anti- viral immunity. The experiments in this proposal will investigate the mechanisms used by flu-specific BRM cells to clear virus and protect the lung and will determine how pulmonary vaccination can elicit and maintain BRM cells in the lung.

项目摘要我们最近确定了新的流感特异性肺居民记忆B细胞（BRM细胞）的新型人群表型上与全身记忆B细胞不同，位于肺中的独特部位，反应更快挑战感染比全身性挑战。有趣的是，肺BRM细胞具有很大的程度保护感染的保护，即使它们不与HA和NA蛋白进行反应挑战病毒，表明BRM细胞具有抗体（AB）生产以外的其他效应功能。实际上，B细胞产生炎症细胞因子，例如IFN，淋巴毒素，OX40L和IL-6，以及抗炎 IL-10，IL-27和IL-35等细胞因子。此外，它们是潜在的APC，尤其是对于其同源抗原。这是BRM细胞除AB以外还具有多种机制，用于调节注射和促进抗病毒免疫。该提案中的实验将研究流感特异性BRM细胞使用的机制清除病毒并保护肺部，并确定肺疫苗接种如何引起和维持BRM 肺中的细胞。