The Role of Basophils in Adaptive Immunity

嗜碱性粒细胞在适应性免疫中的作用

• 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
• 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

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，患病率正在上升，1-4尽管控制IgE应答持续性的机制仍然未确定。嗜碱性粒细胞可以通过在过敏原刺激时表面IgE交联时释放炎性介质来介导过敏效应物应答。还推测它们在鼠模型中的体液应答中起作用，并已显示诱导B细胞产生IgE。我们假设人嗜碱性粒细胞可以诱导人B细胞的IgE，以IgE和活化依赖的方式传播过敏反应。关于持续性IgE产生的起源的争论集中在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细胞的顺序IgE类别转换引起的。嗜碱性粒细胞已被证明运输到淋巴结，我们假设嗜碱性粒细胞可以诱导IgE的生产，从记忆B细胞诱导顺序类转换有效。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使它们将过敏原呈递给B细胞以传播过敏原特异性应答。