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

项目总结： 在美国，免疫球蛋白介导的食物过敏影响大约每13名儿童中就有1名，并在 近几十年来流行。对许多人来说，目前的免疫疗法是无效的，这使得这是一个终生的 严重损害生活质量的疾病。虽然免疫球蛋白E在食物的病理生理学中处于核心地位 过敏，维持高亲和力(致病)IgE的机制还不是很清楚。以前的工作 来自我们实验室的研究表明，小鼠的免疫球蛋白E记忆包含在抗原特异性的群体中 免疫球蛋白G记忆B细胞(MBC)，可发生类转换为IgE。然而，针对广泛的 治疗食物过敏的免疫球蛋白表达细胞亚群因需要保留保护性而变得复杂 对病原体的免疫力。因此，鉴定具有免疫原性的特异性免疫球蛋白MBC非常重要。 以产生高亲和力的IgE反应。这项提案寻求使用花生过敏的小鼠模型来 鉴定免疫表型标记物，区分免疫球蛋白、单核细胞亚群和高表达能力 亲和力IgE浆细胞(PC)。此外，这个应用程序将解决这个细胞命运的可塑性和 Ig G MBC分化为Ig E PC所需的外部信号。最终，我们想要 了解免疫球蛋白单核细胞如何才能成为产生致病免疫球蛋白E的浆细胞，并揭示 可接受治疗干预以改善以下患者生活质量的目标 患有食物过敏症。

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.