High-affinity allergen-specific human antibodies cloned from single IgE B cell transcriptomes
High-affinity allergen-specific human antibodies cloned from single IgE B cell transcriptomes
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DOI：
10.1126/science.aau2599
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发表时间：
2018-12-14
期刊：
影响因子：
56.9
通讯作者：
Quake, Stephen R.
中科院分区：
文献类型：
--
作者：
Croote, Derek;Darmanis, Spyros;Quake, Stephen R.
免疫球蛋白E（IgE）抗体可防止蠕虫感染，但也可引起危及生命的过敏反应。尽管它们在人类健康中起着重要作用，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的例子，其中IgE抗体在无关个体中经历了相同的基因重排。通过获得可变区突变，这些IgE抗体获得了对临床上重要的花生过敏原Ara h 2和Ara h 3的高亲和力和意想不到的交叉反应性。这些发现提供了对IgE B细胞转录组学的深入了解，并使这种抗体类别的生化解剖成为可能。
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.