Food allergy is caused by allergen-specific immunoglobulin E (IgE) antibodies, but little is known about the B cell memory of persistent IgE responses. Here, we describe, in human pediatric peanut allergy, a population of CD23 + IgG1 + memory B cells arising in type 2 immune responses that contain high-affinity peanut-specific clones and generate IgE-producing cells upon activation. The frequency of CD23 + IgG1 + memory B cells correlated with circulating concentrations of IgE in children with peanut allergy. A corresponding population of “type 2–marked” IgG1 + memory B cells was identified in single-cell RNA sequencing experiments. These cells differentially expressed interleukin-4 (IL-4)– and IL-13–regulated genes, such as FCER2 / CD23 + , IL4R , and germline IGHE , and carried highly mutated B cell receptors (BCRs). In children with high concentrations of serum peanut-specific IgE, high-affinity B cells that bind the main peanut allergen Ara h 2 mapped to the population of “type 2–marked” IgG1 + memory B cells and included clones with convergent BCRs across different individuals. Our findings indicate that CD23 + IgG1 + memory B cells transcribing germline IGHE are a unique memory population containing precursors of high-affinity pathogenic IgE-producing cells that are likely to be involved in the long-term persistence of peanut allergy.

中文翻译：

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CD23 + IgG1 + 记忆 B 细胞准备在食物过敏中转而产生致病性 IgE

食物过敏是由过敏原特异性免疫球蛋白 E (IgE) 抗体引起的，但人们对持续 IgE 反应的 B 细胞记忆知之甚少。在这里，我们描述了人类儿科花生过敏中的 CD23 群体+免疫球蛋白G1+记忆 B 细胞在 2 型免疫反应中产生，含有高亲和力花生特异性克隆，并在激活后产生产生 IgE 的细胞。 CD23的频率+免疫球蛋白G1+花生过敏儿童的记忆 B 细胞与循环 IgE 浓度相关。相应的“2 型标记”IgG1 群体+记忆 B 细胞是在单细胞 RNA 测序实验中鉴定出来的。这些细胞差异表达白细胞介素 4 (IL-4) 和 IL-13 调节基因，例如FCER2/CD23 +,IL4R和种系IGHE，并携带高度突变的 B 细胞受体 (BCR)。在血清花生特异性 IgE 浓度较高的儿童中，与主要花生过敏原 Ara h 2 结合的高亲和力 B 细胞映射到“2 型标记”IgG1 群体+记忆 B 细胞，包括不同个体中 BCR 趋同的克隆。我们的研究结果表明 CD23+免疫球蛋白G1+记忆 B 细胞转录种系IGHE是一个独特的记忆群体，含有高亲和力致病性 IgE 产生细胞的前体，这些细胞可能与花生过敏的长期持续存在有关。