Tissue and organ specific human B cell immunity

组织和器官特异性人类 B 细胞免疫

• 批准号: 10265689
• 负责人: Frances E. Lund
• 金额: $ 44.49万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-24 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10265689
• 关键词: Address; Adipose tissue; Affinity; Alabama; Alleles; Alzheimer' s Disease; Antibody Repertoire; Antigens; Asthma; Autoantigens; Autoimmunity; B-Cell Antigen Receptor; B-Lymphocyte Subsets; B-Lymphocytes; Bacteria; Binding; Bioinformatics; Biometry; Blood; Blood Circulation; Brain; Budgets; Carbohydrates; Cardiovascular Diseases; Categories; Cause of Death; Cell Fraction; Cell Lineage; Cell Maintenance; Cell Wall; Cell physiology; Cells; Chronic Disease; Chronic Obstructive Airway Disease; Clinical Research; Cloning; Data; Data Analyses; Data Analytics; Data Files; Data Set; Development; Disease; Epitopes; Exhibits; Failure; Family suidae; Future; Goals; HLA Antigens; Harvest; Heart; Heterogeneity; Heterophile Antigens; Host Defense; Human; Hypersensitivity; Immune; Immune response; Immune system; Immunity; Immunobiology; Immunoglobulin-Secreting Cells; Immunologic Surveillance; Immunology; Immunotherapy; Impairment; Infection; Infection Control; Inflammation; Influenza; Informatics; Intestines; Knowledge; Leukocytes; Link; Lipids; Longevity; Lung; Lymphocyte; Lymphoid; Lymphoid Tissue; Maintenance; Malignant Neoplasms; Maps; Memory B-Lymphocyte; Modeling; Molecular; Mucous Membrane; Organ; Organ Transplantation; Outcome; Peripheral; Phenotype; Phospholipids; Plasma; Play; Polysaccharides; Population; Prevalence; Process; Property; Rapid screening; Reagent; Regimen; Research; Research Design; Role; Sampling; Services; Site; Specificity; T-Lymphocyte; Testing; Time; Tissue Banks; Tissue Donors; Tissues; Transplantation; Vaccination; Viral Antigens; Virus; Visualization software; Work; Xenograft procedure; adaptive immune response; adaptive immunity; analytical tool; biobank; biodefense; cancer cell; design; experience; experimental study; flu; human tissue; improved; mouse model; natural antibodies; novel; novel vaccines; pathogen; preservation; prevent; programs; repository; technology development; tool; transcriptome; translational study

Overall: Tissue and organ-specific human B cell immunity Project Summary Experiments conducted using genetically modified mice and model pathogens or antigens have shaped our current understanding of adaptive immunity. From these studies, it is clear that both B and T cell immunity is exquisitely tailored to the pathogen or antigen. Furthermore, the data show that adaptive immune responses in lymphoid and peripheral tissues, which are found in both mucosal and systemic sites, can differ dramatically. Thus, we now know that studying immunity in a single lymphoid tissue to model antigens, while informative, does not reveal the full complexity of the adaptive immune response. This lesson, learned using mouse models, can also be applied to human immune responses. To date, the vast majority of human immune responses have only been queried in the blood. This approach has not only limited our analysis to the lymphocytes that are in circulation but has also restricted us to examining a small fraction of the cells (typically 1-2%) that are in circulation at a given time. This “limited sampling approach” has also impaired our capacity to examine antigen- specific lymphocytes as these cells are rare populations, even during an ongoing immune response, and are largely undetectable under homeostatic conditions. Thus, we know exceedingly little about the phenotype, molecular programming, lifespan and function of human immune cells that reside primarily in tissues under homeostatic conditions. Moreover, we know essentially nothing about the clonal connections between antigen- specific cells in the different tissues of the human body. These represent fundamental gaps in our basic knowledge of the human immune system and reduce our ability to design new vaccines to prevent emerging infections, to create immunotherapies that can be used to treat cancer, autoimmunity and chronic disease and to develop tolerance-inducing regimens that will improve transplantation outcomes. Therefore, the overall goal of this U19 Program is to determine the molecular and functional relationships between human memory B lymphocyte and antibody secreting cell (ASC) populations that are found in pulmonary, intestinal and adipose tissues under homeostatic conditions. This U19 Program, which is composed of three Projects and three scientific Cores, will test our central hypothesis that antigen-specific, antigen-experienced human tissue-residing B cells are heterogeneous with respect to phenotype, transcriptome, breadth of reactivity, and function. We expect our studies to reveal the identity of novel subsets of antigen-experienced B cells exhibiting unique tissue- specific “signatures”. This outcome will inform future studies of fundamental basic human immunobiology and is likely to influence future translational and clinical studies, as B cells specific for the viral antigens and bacterial cell wall components are important targets for vaccination and are required for host defense against a number of different Biodefense Category A and C pathogens.

总体而言：组织和器官特异性人类 B 细胞免疫 项目概要 使用转基因小鼠和模型病原体或抗原进行的实验塑造了我们的 从这些研究中可以看出，B 细胞免疫和 T 细胞免疫都是目前对适应性免疫的认识。 此外，数据显示，适应性免疫反应可以针对病原体或抗原进行精心定制。 粘膜和全身部位的淋巴组织和外周组织可能存在显着差异。 因此，我们现在知道，研究单个淋巴组织中的免疫来模拟抗原，虽然信息丰富，但确实 使用小鼠模型学到的这一教训并不能揭示适应性免疫反应的全部复杂性。 也可应用于人类免疫反应，迄今为止，绝大多数人类免疫反应仅具有。 这种方法不仅限制了我们对血液中淋巴细胞的分析。 但也限制了我们只能检查一小部分细胞（通常为 1-2%） 这种“有限采样方法”也削弱了我们检查抗原的能力。 特定淋巴细胞，因为这些细胞是稀有群体，即使在持续的免疫反应期间也是如此，并且 在稳态条件下基本上无法检测到，因此，我们对表型知之甚少。 主要存在于组织中的人类免疫细胞的分子编程、寿命和功能 此外，我们对抗原之间的克隆联系基本上一无所知。 人体不同组织中的特定细胞代表了我们基本的根本差距。 对人类免疫系统的了解并降低了我们设计新疫苗以预防新出现的疾病的能力 感染，创造可用于治疗癌症、自身免疫和慢性疾病的免疫疗法， 因此，总体目标是开发能够改善移植结果的耐受诱导方案。 该 U19 计划的目的是确定人类记忆 B 之间的分子和功能关系 肺部、肠道和脂肪中发现的淋巴细胞和抗体分泌细胞 (ASC) 群 该 U19 计划由三个项目和三个组成。 科学核心，将测试我们的中心假设，即抗原特异性、经历过抗原的人体组织中存在 B 细胞在表型、转录组、反应范围和功能方面具有异质性。 希望我们的研究能够揭示经历过抗原的 B 细胞新亚群的身份，这些亚群表现出独特的组织- 这一结果将为未来的基本人类免疫生物学研究提供信息。 可能会影响未来的转化和临床研究，因为 B 细胞对病毒抗原和细菌具有特异性 细胞壁成分是疫苗接种的重要目标，是宿主防御多种疾病所必需的。 不同的生物防御 A 类和 C 类病原体。