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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：
10410377
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/10410377
关键词：
Affinity Anti-Inflammatory Agents Antibodies Antibody Formation 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 Interleukin-10 Interleukin-6 Ligands Longevity Lung Lymphoid Tissue Maintenance Mediating Memory B-Lymphocyte Peripheral Phenotype Population Proliferating Property Proteins Pulmonary Inflammation Reaction 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.

项目摘要我们最近发现了一种新的流感特异性肺部记忆B细胞（BRM细胞），表型上不同于全身记忆B细胞，存在于肺中的独特部位，反应更迅速更能对抗感染有趣的是，肺BRM细胞提供了显著程度的保护挑战感染，即使当他们不交叉反应的HA和NA蛋白的攻击病毒，表明BRM细胞具有除抗体（Ab）产生之外的额外效应子功能。事实上，B细胞产生炎性细胞因子如IFN γ、光氧合酶、OX 40 L和IL-6，以及抗炎性细胞因子。细胞因子如IL-10、IL-27和IL-35。此外，它们是有效的APC，特别是对于它们的同源抗原。因此，BRM细胞除了Ab外，还具有多种机制来调节炎症并促进抗肿瘤作用。病毒免疫本实验将研究流感特异性BRM细胞的作用机制以清除病毒和保护肺部，并将确定肺部疫苗接种如何引发和维持BRM 肺里的细胞