Characterizing the IgG1 Memory B cells that are precursors of pathogenic IgE

表征作为致病性 IgE 前体的 IgG1 记忆 B 细胞

• 批准号: 10725159
• 负责人: Jamie Redes
• 金额: $ 4.61万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-03 至 2025-08-02
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10725159
• 关键词: Address; Adoptive Cell Transfers; Affect; Affinity; Allergens; Allergic Reaction; Allergy to peanuts; Anaphylaxis; Antibodies; Antigens; B cell differentiation; B-Lymphocyte Subsets; B-cell receptor repertoire sequencing; Binding; Biological; CD80 gene; CRISPR/Cas technology; Cell Degranulation; Cell surface; Cells; Cellular Indexing of Transcriptomes and Epitopes by Sequencing; Characteristics; Child; Circulation; Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; Cues; Data; Detection; Disease; Exposure to; Flow Cytometry; Food; Food Hypersensitivity; Functional disorder; Genetic Engineering; Genetic Transcription; Growth; Gut Mucosa; Heterogeneity; Human; Hypersensitivity; IgE; IgG1; Immunity; Immunize; Immunoglobulin Class Switching; Immunoglobulin G; Immunophenotyping; Immunotherapeutic agent; Immunotherapy; Impairment; Individual; Laboratories; Life; Lymphoid Tissue; Mediating; Memory; Memory B-Lymphocyte; Milk; Mission; Modeling; Molecular; Mus; National Institute of Allergy and Infectious Disease; Outcome; Outcome Study; Pathogenicity; Pathway interactions; Patients; Phenotype; Plasma Cells; Play; Population; Prevalence; Probability; Process; Production; Public Health; Quality of life; Research; Research Personnel; Risk; Role; Signal Transduction; Structure of germinal center of lymph node; Surface; System; Techniques; Testing; Therapeutic Intervention; Tissue Stains; Tissues; Trust; Variant; Work; career; cell motility; cytokine; differential expression; egg; food allergen; improved; in vivo; mast cell; mouse model; new therapeutic target; novel; pathogen; response; selective expression; single-cell RNA sequencing; training opportunity

PROJECT SUMMARY: IgE-mediated food allergy affects approximately 1 in 13 children in the USA and has continued to grow in prevalence in recent decades. For many, current immunotherapies are ineffective, making this is a lifelong disease with significant impairment in quality of life. Although IgE is central to the pathophysiology of food allergy, the mechanisms maintaining high affinity (pathogenic) IgE are not well understood. Previous work from our laboratory has shown that IgE memory in mice is contained within a population of antigen-specific IgG memory B cells (MBC) that can undergo class switching to IgE. However, strategies targeting a broad subset of IgG-expressing cells for treatment of food allergy is complicated by the need to retain protective immunity against pathogens. Therefore, it is important to identify the specific IgG MBC that have the ability to generate high affinity IgE responses. This proposal seeks to use mouse models of peanut allergy to identify immunophenotypic markers that can distinguish IgG MBC subsets with the ability to produce high affinity IgE plasma cells (PC). In addition, this application will address the plasticity of this cell fate and the external signals that are required for IgG MBC differentiation into IgE PC. Ultimately, we want to understand what it takes for an IgG MBC to become a pathogenic-IgE producing plasma cell and reveal targets that could be amenable to therapeutic intervention to improve the quality of life of patients who suffer from food allergies.

项目摘要： IgE介导的食物过敏会影响美国大约13名儿童，并继续增长 近几十年以来的流行。对于许多人来说，当前的免疫疗法是无效的，这是终生的 生活质量严重损害的疾病。尽管IgE是食物病理生理学的核心 过敏，维持高亲和力（致病）IgE的机制尚不清楚。以前的工作 从我们的实验室中表明，小鼠的IgE记忆包含在抗原特异性的种群中 IgG内存B单元（MBC）可以进行类切换到IgE的类别。但是，针对广泛的策略 以保留保护性的需要，用于治疗食物过敏的表达IgG细胞的子集很复杂 对病原体的免疫力。因此，重要的是确定具有能力的特定IgG MBC 产生高亲和力的响应。该建议旨在使用花生过敏的鼠标模型 确定可以区分IgG MBC子集的免疫表型标记 亲和力IgE浆细胞（PC）。此外，此应用将解决该细胞命运的可塑性和 IgG MBC分化为IgE PC所需的外部信号。最终，我们想 了解IgG MBC成为一种致病性产生的浆细胞并揭示的需要 可以接受治疗干预的目标，以提高患者的生活质量 患有食物过敏。