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B cell memory in human food allergy

人类食物过敏中的 B 细胞记忆

基本信息

批准号：
10306255
负责人：
MARIA A CUROTTO DE LAFAILLE
金额：
$ 75.97万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
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/10306255
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 Goals Human Hypersensitivity IL4R gene IgE IgG1 Immune Immunoglobulin Class Switching Immunoglobulin G In Vitro Individual Inflammatory Institutes Life Mediating Mediator of activation protein Memory Memory B-Lymphocyte Milk Modeling Molecular Profiling Mus Pathogenicity Phenotype Plasma Cells Population Proteins Publishing Research Resolution Risk Role Tetanus Transcript Vaccine Antigen Viral Antigens Viral Vaccines atopy base clinical care comparative design experimental study food allergen inflammatory disease of the intestine influenzavirus longitudinal analysis new therapeutic target novel therapeutics patient population response single-cell RNA sequencing targeted treatment tool transcriptomics

项目摘要

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