B cell memory in human food allergy

人类食物过敏中的 B 细胞记忆

• 批准号: 10632078
• 负责人: MARIA A CUROTTO DE LAFAILLE
• 金额: $ 75.84万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-09 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10632078
• 关键词: Affect; Affinity; Allergens; Allergic; Allergic Disease; Anaphylaxis; Antibodies; Antibody Response; Asthma; Atopic Dermatitis; B-Cell Activation; B-Lymphocytes; Basic Science; Blood; Cells; Cellular Indexing of Transcriptomes and Epitopes by Sequencing; Characteristics; Child; Childhood; Clinical Research; Cytometry; Data; Development; Diphtheria Toxoid; Disease; Environment; Evolution; Food; Food Hypersensitivity; Food Supply; Food production; Generations; Genes; Goals; Human; Hypersensitivity; IL13RA1 gene; IL4R gene; IgE; IgG1; Immune; Immunoglobulin Class Switching; Immunoglobulin G; In Vitro; Individual; Inflammatory; Institution; Life; Mediating; Mediator; Memory; Memory B-Lymphocyte; Milk; Modeling; Molecular Profiling; Mus; Pathogenicity; Phenotype; Plasma Cells; Population; Proliferating; Proteins; Publishing; Reaction; Research; Resolution; Risk; Risk Marker; Role; Tetanus; Transcript; Vaccine Antigen; Viral; Viral Antigens; atopy; clinical care; comparative; design; experimental study; food allergen; gut inflammation; influenzavirus; longitudinal analysis; new therapeutic target; novel therapeutics; patient population; response; single-cell RNA sequencing; targeted treatment; tool; transcriptomics

Summary High affinity IgE antibodies are essential mediators of food allergy, a main cause of life-threatening anaphylaxis. Most food allergies develop in childhood and affect children disproportionally. A long-standing question in the allergy field is why allergies to some foods spontaneously cure, while others persist. A key to understanding the evolution of food allergy may reside in the mechanisms that maintain the B cell memory of high affinity IgE responses. Experimental studies from our group demonstrated that IgE cells exist mostly as plasma cells and not IgE memory cells, and that high affinity pathogenic IgE antibodies derive from the sequential switching of affinity matured IgG1 memory B cells. While the origin of human high affinity IgE is not definitely proved, an increasing body of work supports a precursor role of IgG memory cells in the generation of human pathogenic IgE plasma cells. We hypothesize that the existence of high affinity food-specific IgG cells and their ability to undergo class switching to IgE are critical for allergy persistence. Preliminary studies from our group suggest that atopic individuals harbor B lymphocytes with a distinct profile that increases their response to activation and differentiation into IgE plasma cells. We postulate that the atopic immune environment marks allergen-specific IgG memory cells with a ‘pro-allergic’ signature, and that the presence of these pro-allergic memory cells is necessary for the development and persistence of food allergy. We propose to investigate the existence of pro- allergic memory B lymphocytes in food allergic children, in children that outgrew their food allergy, in tolerant never-allergic children, and in children with non-allergic inflammatory disease. We will determine if memory B cells that recognize food allergens have a specific phenotype that distinguish them from memory B cells that recognize virus and vaccines antigens in allergic and non-allergic children. We expect that the findings from this study will provide tools to predict food-allergy risk and persistence, and help to design new therapies for allergic diseases.

总结 高亲和力IgE抗体是食物过敏的基本介质，食物过敏是危及生命的过敏反应的主要原因。 大多数食物过敏发生在儿童时期，并对儿童产生不良影响。一个长期存在的问题 过敏领域是为什么过敏的一些食物自发治愈，而其他人坚持。理解这一点的关键是 食物过敏的进化可能存在于维持B细胞对高亲和力IgE记忆的机制中 应答我们小组的实验研究表明，IgE细胞主要以浆细胞存在， 而不是IgE记忆细胞，高亲和力致病性IgE抗体来源于 亲和力成熟的IgG 1记忆B细胞。虽然人类高亲和力IgE的起源尚未明确证明，但在某些情况下， 越来越多的工作支持IgG记忆细胞在人类致病性免疫缺陷病毒产生中的前体作用。 IgE浆细胞。我们假设高亲和力食物特异性IgG细胞的存在和它们的能力， 经历IgE的类别转换对于过敏持续性至关重要。我们小组的初步研究表明 特应性个体具有独特的B淋巴细胞特征，这种特征增加了它们对活化的反应， 分化为IgE浆细胞。我们推测，特应性免疫环境标志着过敏原特异性 IgG记忆细胞具有“促过敏”特征，并且这些促过敏记忆细胞的存在是 食物过敏的发展和持续所必需的。我们建议调查亲- 过敏记忆B淋巴细胞在食物过敏儿童中，在食物过敏儿童中， 从未过敏的儿童，以及患有非过敏性炎症性疾病的儿童。我们将确定内存B 识别食物过敏原的细胞具有一种特殊的表型，将它们与记忆B细胞区分开来， 识别过敏和非过敏儿童的病毒和疫苗抗原。我们希望这次调查的结果 这项研究将提供预测食物过敏风险和持续性的工具，并帮助设计新的过敏治疗方法。 疾病