Ota Miyo, Hoehn Kenneth B, Ota Takayuki, Aranda Carlos J, Friedman Sara, Braga Weslley F, Malbari Alefiyah, Kleinstein Steven H, Sicherer Scott H, Curotto de Lafaille Maria A
bioRxiv. 2023 Jan 25:2023.01.25.525506. doi: 10.1101/2023.01.25.525506.
Food allergy is caused by allergen-specific IgE antibodies but little is known about the B cell memory of persistent IgE responses. Here we describe in human pediatric peanut allergy CD23 IgG1 memory B cells arising in type 2 responses that contain peanut specific clones and generate IgE cells on activation. These 'type2-marked' IgG1 memory B cells differentially express IL-4/IL-13 regulated genes / , and germline and carry highly mutated B cell receptors (BCRs). Further, high affinity memory B cells specific for the main peanut allergen Ara h 2 mapped to the population of 'type2-marked' IgG1 memory B cells and included convergent BCRs across different individuals. Our findings indicate that CD23 IgG1 memory B cells transcribing germline are a unique memory population containing precursors of pathogenic IgE.
ONE-SENTENCE SUMMARY: We describe a unique population of IgG memory B cells poised to switch to IgE that contains high affinity allergen-specific clones in peanut allergy.
食物过敏由过敏原特异性IgE抗体引起，但对于持续性IgE反应的B细胞记忆了解甚少。在此，我们描述了在人类儿童花生过敏中，在2型反应中产生的CD23+IgG1+记忆B细胞，这些细胞包含花生特异性克隆，并在激活时产生IgE细胞。这些“2型标记”的IgG1+记忆B细胞差异性地表达IL-4/IL-13调控基因，并且带有种系基因，同时携带高度突变的B细胞受体（BCR）。此外，对主要花生过敏原Ara h 2特异的高亲和力记忆B细胞定位于“2型标记”的IgG1+记忆B细胞群体中，并且包括不同个体间趋同的BCR。我们的研究结果表明，转录种系基因的CD23+IgG1+记忆B细胞是一个独特的记忆群体，包含致病性IgE的前体。
我们描述了一类独特的IgG记忆B细胞群体，它们准备转换为IgE，在花生过敏中包含高亲和力过敏原特异性克隆。
