B cell memory in human food allergy

摘要 高亲和力的IgE抗体是食物过敏的重要媒介，食物过敏是威胁生命的过敏反应的主要原因。 大多数食物过敏是在儿童时期发展起来的，对儿童的影响不成比例。这是一个长期存在的问题 过敏症领域是为什么对一些食物的过敏会自发治愈，而对其他食物的过敏会持续下去。理解的关键是 食物过敏的进化可能存在于维持高亲和力IgE的B细胞记忆的机制中 回应。本课题组的实验研究表明，IgE细胞主要以浆细胞的形式存在， 而不是IgE记忆细胞，高亲和力致病IgE抗体源于 亲和成熟的IgG1Memory B细胞。虽然人类高亲和力IgE的起源尚不确定，但一种 越来越多的工作支持了免疫球蛋白记忆细胞在人类致病性疾病发生中的先驱作用 IGE浆细胞。我们假设高亲和力食物特异性免疫球蛋白细胞的存在和它们的能力 进行班级转换为IgE对过敏持久性至关重要。我们小组的初步研究表明 特应性患者体内的B淋巴细胞具有独特的特征，可以增强他们对激活和 分化为IgE浆细胞。我们推测，特应性免疫环境标志着过敏原特异性 具有“亲过敏”特征的免疫球蛋白记忆细胞，而这些促过敏记忆细胞的存在是 对于食物过敏的发展和持久性是必要的。我们建议调查是否存在亲- 食物过敏儿童中的过敏记忆B淋巴细胞，对食物过敏的儿童，在耐受性中 从不过敏的儿童，以及患有非过敏性炎症性疾病的儿童。我们将确定内存B 识别食物过敏原的细胞具有特定的表型，将它们与记忆B细胞区分开来 识别过敏性和非过敏性儿童的病毒和疫苗抗原。我们预计这一调查结果 这项研究将提供预测食物过敏风险和持久性的工具，并有助于设计新的过敏疗法 疾病。

Summary High affinity IgE antibodies are essential mediators of food allergy, a main cause of life-threatening anaphylaxis. Most food allergies develop in childhood and affect children disproportionally. A long-standing question in the allergy field is why allergies to some foods spontaneously cure, while others persist. A key to understanding the evolution of food allergy may reside in the mechanisms that maintain the B cell memory of high affinity IgE responses. Experimental studies from our group demonstrated that IgE cells exist mostly as plasma cells and not IgE memory cells, and that high affinity pathogenic IgE antibodies derive from the sequential switching of affinity matured IgG1 memory B cells. While the origin of human high affinity IgE is not definitely proved, an increasing body of work supports a precursor role of IgG memory cells in the generation of human pathogenic IgE plasma cells. We hypothesize that the existence of high affinity food-specific IgG cells and their ability to undergo class switching to IgE are critical for allergy persistence. Preliminary studies from our group suggest that atopic individuals harbor B lymphocytes with a distinct profile that increases their response to activation and differentiation into IgE plasma cells. We postulate that the atopic immune environment marks allergen-specific IgG memory cells with a ‘pro-allergic’ signature, and that the presence of these pro-allergic memory cells is necessary for the development and persistence of food allergy. We propose to investigate the existence of pro- allergic memory B lymphocytes in food allergic children, in children that outgrew their food allergy, in tolerant never-allergic children, and in children with non-allergic inflammatory disease. We will determine if memory B cells that recognize food allergens have a specific phenotype that distinguish them from memory B cells that recognize virus and vaccines antigens in allergic and non-allergic children. We expect that the findings from this study will provide tools to predict food-allergy risk and persistence, and help to design new therapies for allergic diseases.