IgE B cells unmasked Immunoglobulin E (IgE) antibodies play a central role in immune responses against helminth and protozoan parasites; however, they also contribute to allergies. IgE antibodies (and the B cells generating them) are rare and thus poorly characterized. Croote et al. performed single-cell RNA sequencing of peripheral blood B cells from patients with peanut allergies and delineated each cell's gene expression, splice variants, and antibody sequences (see the Perspective by Gould and Ramadani). Unlike other isotypes, circulating IgE B cells were mostly immature plasmablasts. Surprisingly, certain IgE antibodies manifested identical gene rearrangements in unrelated individuals. These IgE antibodies showed high affinity and unexpected cross-reactivity to peanut allergens. Science, this issue p. 1306; see also p. 1247 Single-cell sequencing of IgE B cells from allergic individuals reveals surprising insights. Immunoglobulin E (IgE) antibodies protect against helminth infections but can also cause life-threatening allergic reactions. Despite their role in human health, the cells that produce these antibodies are rarely observed and remain enigmatic. We isolated single IgE B cells from individuals with food allergies and used single-cell RNA sequencing to elucidate the gene expression and splicing patterns unique to these cells. We identified a surprising example of convergent evolution in which IgE antibodies underwent identical gene rearrangements in unrelated individuals. Through the acquisition of variable region mutations, these IgE antibodies gained high affinity and unexpected cross-reactivity to the clinically important peanut allergens Ara h 2 and Ara h 3. These findings provide insight into IgE B cell transcriptomics and enable biochemical dissection of this antibody class.

中文翻译：

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从单个 IgE B 细胞转录组克隆的高亲和力过敏原特异性人抗体

IgE B 细胞暴露的免疫球蛋白 E (IgE) 抗体在针对蠕虫和原生动物寄生虫的免疫反应中发挥核心作用；然而，它们也会导致过敏。IgE 抗体（以及产生它们的 B 细胞）很少见，因此很难表征。克鲁特等人。对花生过敏患者的外周血 B 细胞进行单细胞 RNA 测序，并描绘出每个细胞的基因表达、剪接变异和抗体序列（参见 Gould 和 Ramadani 的观点）。与其他同种型不同，循环 IgE B 细胞主要是未成熟的浆母细胞。令人惊讶的是，某些 IgE 抗体在无关个体中表现出相同的基因重排。这些 IgE 抗体对花生过敏原表现出高亲和力和意想不到的交叉反应性。科学，这个问题 p。1306; 另见第。1247 来自过敏个体的 IgE B 细胞的单细胞测序揭示了令人惊讶的见解。免疫球蛋白 E (IgE) 抗体可防止蠕虫感染，但也会引起危及生命的过敏反应。尽管它们在人类健康中发挥作用，但产生这些抗体的细胞很少被观察到并且仍然是个谜。我们从食物过敏的个体中分离出单个 IgE B 细胞，并使用单细胞 RNA 测序来阐明这些细胞特有的基因表达和剪接模式。我们发现了一个令人惊讶的趋同进化例子，其中 IgE 抗体在无关个体中经历了相同的基因重排。通过可变区突变的获取，