Increased IgE is a typical feature of allergic rhinitis. Local class-switch recombination has been intimated but B cell precursors and mechanisms remain elusive. Here we describe the dynamics underlying the generation of IgE-antibody secreting cells (ASC) in human nasal polyps (NP), mucosal tissues rich in ASC without germinal centers (GC). Using V_H next generation sequencing, we identified an extrafollicular (EF) mucosal IgD+ naïve-like intermediate B cell population with high connectivity to the mucosal IgE ASC. Mucosal IgD+ B cells, express germline epsilon transcripts and predominantly co-express IgM. However, a small but significant fraction co-express IgG or IgA instead which also show connectivity to ASC IgE. Phenotypically, NP IgD+ B cells display an activated profile and molecular evidence of BCR engagement. Transcriptionally, mucosal IgD+ B cells reveal an intermediate profile between naïve B cells and ASC. Single cell IgE ASC analysis demonstrates lower mutational frequencies relative to IgG, IgA, and IgD ASC consistent with IgE ASC derivation from mucosal IgD+ B cell with low mutational load. In conclusion, we describe a novel mechanism of GC-independent, extrafollicular IgE ASC formation at the nasal mucosa whereby activated IgD+ naïve B cells locally undergo direct and indirect (through IgG and IgA), IgE class switch.

IgE升高是过敏性鼻炎的典型特征。局部类别转换重组已被证实，但 B 细胞前体和机制仍然难以捉摸。在这里，我们描述了人鼻息肉 (NP) 中 IgE 抗体分泌细胞 (ASC) 生成的动力学，鼻息肉是富含 ASC 的粘膜组织，没有生发中心 (GC)。使用V _H在下一代测序中，我们发现了一个滤泡外 (EF) 粘膜 IgD+ 幼稚样中间 B 细胞群，与粘膜 IgE ASC 具有高度连接性。粘膜 IgD+ B 细胞，表达种系 epsilon 转录物并主要共表达 IgM。然而，一小部分但重要的部分共表达 IgG 或 IgA，它们也显示出与 ASC IgE 的连接性。从表型上看，NP IgD+ B 细胞显示出激活的特征和 BCR 参与的分子证据。在转录方面，粘膜 IgD+ B 细胞显示出介于幼稚 B 细胞和 ASC 之间的中间特征。单细胞 IgE ASC 分析表明相对于 IgG、IgA 和 IgD ASC 的突变频率较低，这与从具有低突变负荷的粘膜 IgD+ B 细胞衍生的 IgE ASC 一致。总之，我们描述了一种与 GC 无关的新机制，