Cellular and molecular mechanisms of IgE cell memory in allergic responses

过敏反应中IgE细胞记忆的细胞和分子机制

• 批准号: 9891945
• 负责人: MARIA A CUROTTO DE LAFAILLE
• 金额: $ 52.61万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9891945
• 关键词: Address; Adhesions; Affinity; Allergens; Allergic; Allergic Disease; Allergic Reaction; Anaphylaxis; Antibodies; Antibody Affinity; Antibody Formation; Antibody Response; Antibody-Producing Cells; Antigens; Apoptotic; B-Lymphocyte Subsets; B-Lymphocytes; Biological; Bone Marrow; CD80 gene; Cell Differentiation process; Cells; Cellular biology; Cessation of life; Data; Development; Exposure to; Food Hypersensitivity; Generations; Genetic; Goals; IgE; IgG1; Immunize; Immunoglobulin Class Switching; Immunoglobulin G; Kinetics; Laboratories; Lead; Life; Longevity; Mediating; Mediator of activation protein; Memory; Memory B-Lymphocyte; Molecular; Outcome; Pathogenicity; Pathway interactions; Patients; Persons; Plasma Cells; Plasmablast; Population; Process; Production; Property; Regulation; Risk; Spleen; Structure of germinal center of lymph node; Therapeutic Intervention; Work; allergic response; base; experimental study; fitness; lymphoid organ; mast cell; migration; prevent; programs; response; targeted treatment

Project Summary: IgE antibodies are essential mediators of allergic reactions. Small amounts of allergen-specific IgE can cause life-threatening anaphylaxis, but anaphylaxis can be prevented by non-specific or low affinity IgE. Understanding the mechanisms that control the production of high affinity and low affinity IgE is thus of outmost importance for the development targeted therapies. Previous work from our laboratory demonstrated that IgE cells do not follow the classical differentiation pathway that has been well described for IgG cells. IgE germinal center cells are transient and apoptotic, and fail to generate long lived plasma cells and functional IgE memory cells. Nevertheless, high affinity IgE can be generated by the sequential switching of IgG1 cells to IgE. The mechanisms that maintain the memory of IgE responses are poorly understood. Long-term antibody responses, typically those involving IgG antibodies, are maintained by memory B cells that are reactivated upon re-exposure to antigen, and by long lived plasma cells. It is clear that the mechanisms of memory of IgE responses must be unique and different from IgG memory. In this application, we will address the long-lasting question of the cellular origin of high and low affinity IgE in memory responses. Ultimately we want to understand what it takes to make pathogenic IgE, and define steps in the process that could be amenable to therapeutic intervention.

项目摘要： IgE抗体是过敏反应的基本介体。少量过敏原特异性IgE可能导致 危险过敏反应，但是通过非特异性或低亲和力IgE可以预防过敏反应。 因此了解控制高亲和力和低亲和力生产的机制是 对于开发疗法而言，最重要的是。我们实验室的先前工作证明了 IgE细胞不遵循已对IgG细胞进行很好描述的经典分化途径。 Ige 生发中心细胞是短暂的和凋亡的，无法产生长期生存的浆细胞和功能性IgE 记忆单元。然而，通过IgG1细胞向IgE的顺序切换，可以产生高亲和力IgE。 维持IgE反应记忆的机制知之甚少。长期抗体 响应，通常是涉及IgG抗体的响应，由已重新激活的存储B细胞维持 重新暴露于抗原并被长期寿命的浆细胞接触。显然，IgE记忆的机制 响应必须独特，并且与IgG内存不同。在此应用程序中，我们将解决持久的 在记忆反应中高和低亲和力IgE的细胞起源问题。最终我们想 了解制造病原IgE的需要，并在过程中定义步骤 治疗干预。