The Role of Basophils in Adaptive Immunity

嗜碱性粒细胞在适应性免疫中的作用

基本信息

批准号：
8456533
负责人：
Sarita U Patil
金额：
$ 5.94万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8456533
关键词：
Address Affect Affinity Allergens Allergic Allergic Disease Antibodies Antibody Formation Antigen-Presenting Cells Antigens Asthma Atopic Dermatitis B-Lymphocytes Basophils Cell Line Cells Chemicals Clonality Complex Disease Effector Cell Endocytosis Environment Food Hypersensitivity Health Histamine Human Human Characteristics Hypersensitivity IgE Immediate hypersensitivity Immunization Immunoglobulin Class Switching Immunoglobulin G In Vitro Individual Inflammation Mediators Inflammatory Interleukin-13 Interleukin-4 Interleukin-6 Leukemic Cell Mediating Mediator of activation protein Memory B-Lymphocyte Modeling Mus Natural History Pathogenesis Play Prevalence Process Production Rattus Reaction Research Role Structure of germinal center of lymph node Surface TNFSF5 gene United States adaptive immunity allergic response crosslink cytokine human disease insight lymph nodes public health relevance response rhinoconjunctivitis trafficking

项目摘要

DESCRIPTION (provided by applicant): IgE-mediated allergic diseases, including allergic rhinoconjunctivitis and food allergies, are rising in prevalence,1-4 though the mechanisms that govern the persistence of IgE responses continue to remain unidentified. Basophils can mediate allergic effector responses by releasing inflammatory mediators on cross-linking of surface IgE on allergen stimulation. They have also been speculated to play a role in humoral responses in murine models and have been shown to induce IgE production from B cells. We hypothesize that human basophils can induce IgE from human B cells to propagate the allergic response in an IgE and activation dependent manner. Controversy on the origin of persistent IgE production centers on whether IgE is produced by IgE memory B cells originating from germinal centers or results from sequential IgE class switching from IgG producing memory B cells. Basophils have been shown to traffic to lymph nodes, and we hypothesize that basophils can induce IgE production from memory B cells by induction of sequential class switching efficiently. We further speculate that the ability of basophils to endocytose allergen in an IgE mediated fashion may also allow them to present allergens to B cells to propagate an allergen-specific response.

描述（由申请人提供）：IgE 介导的过敏性疾病，包括过敏性鼻结膜炎和食物过敏，其患病率正在上升，1-4，但控制 IgE 反应持续性的机制仍不清楚。嗜碱性粒细胞可以通过在过敏原刺激下表面 IgE 交联释放炎症介质来介导过敏效应反应。它们还被推测在小鼠模型的体液反应中发挥作用，并且已被证明可以诱导 B 细胞产生 IgE。我们假设人类嗜碱性粒细胞可以诱导人类 B 细胞产生 IgE，以 IgE 和激活依赖性方式传播过敏反应。关于持久性 IgE 产生的起源的争议集中在 IgE 是由源自生发中心的 IgE 记忆 B 细胞产生的，还是由产生 IgG 的记忆 B 细胞连续 IgE 类别转换的结果。嗜碱性粒细胞已被证明可以运输到淋巴结，我们假设嗜碱性粒细胞可以通过有效诱导顺序类别转换来诱导记忆 B 细胞产生 IgE。我们进一步推测嗜碱性粒细胞以 IgE 介导的方式内吞过敏原的能力也可能允许它们将过敏原呈递给 B 细胞以传播过敏原特异性反应。