杭州浙大迪迅生物基因工程有限公司

原标题：过敏原特异性IgG+记忆B细胞与IgE记忆应答短暂相关
　　①人体中的IgE在所有免疫球蛋白中含量最少，受到严格的调控，产生IgE的B细胞较少。IgE应答的细胞起源和进化目前尚不清楚。②目的：探讨通过舌下免疫治疗(SLIT)，黏膜受到过敏原刺激后，IgE记忆应答的细胞和克隆来源。③在一项随机双盲、安慰剂对照、时程SLIT（舌下免疫治疗）研究中，分别在基线、4周、8周、16周、28周和52周时，采集40名季节性过敏性鼻炎患者的外周血单核细胞(PBMCs)和鼻活组织切片，从外周血单核细胞中提取RNA，分选B细胞和鼻活组织切片进行VH测序。此外，单克隆抗体来源于单一的B细胞转录组。④结合VH测序和单细胞转录组学发现了直接证据，证明了存活短暂的IgE+浆母细胞和IgG+记忆B细胞(称为IgGE)的两个同源且功能相关的B细胞亚群的平行增加。通过SLIT，粘膜草花粉过敏原暴露导致IgE和IgGE序列高度多样化。根据重链同型、体细胞超突变和克隆组成，这些基因发生了广泛的突变，并表现出相对的稳定性。单个IgGE +记忆B细胞和IgE+ 前浆母细胞转录组编码的抗体是针对主要草花粉过敏原的，能够在极低的过敏原浓度下诱导嗜碱性粒细胞活化。⑤我们首次发现，在粘膜暴露于过敏原时，人的IgE记忆存在于过敏原特异性IgG+记忆B细胞中。这些细胞快速转换亚型并扩展为存活短暂的IgE+ 浆母细胞，成为治疗干预的潜在靶点。
延伸阅读
JACI
Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses
https://doi.org/10.1016/j.jaci.2019.11.046
Background
Immunoglobulin E (IgE) are least abundant, tightly regulated and IgE producing B cells are rare. The cellular origin and evolution of IgE responses are poorly understood.
Objective
To investigate the cellular and clonal origin of IgE memory responses following mucosal allergen exposure by sublingual immunotherapy (SLIT).
Methods
In a randomized double-blind, placebo-controlled, time-course SLIT study, peripheral blood mononuclear cells (PBMCs) and nasal biopsies were collected from forty adults with seasonal allergic rhinitis at baseline, 4, 8, 16, 28 and 52 weeks. RNA was extracted from PBMCs, sorted B cells and nasal biopsies for VH repertoire sequencing. Moreover, monoclonal antibodies were derived from single B cell transcriptomes.
Results
Combining VH repertoire sequencing and single cell transcriptomics yielded direct evidence of a parallel boost of two clonally and functionally related B cell subsets of short-lived IgE+ plasmablasts and IgG+ memory B cells (termed IgGE). Mucosal grass pollen allergen exposure by SLIT resulted in highly diverse IgE and IgGE repertoires. These were extensively mutated and appeared relative stable as per heavy chain isotype, somatic hypermutations and clonal composition. Single IgGE + memory B cell and IgE+ pre-plasmablast transcriptomes encoded antibodies that were specific for major grass pollen allergens and were able to elicit basophil activation at very low allergen concentrations. 
Conclusion
For the first time, we have shown that upon mucosal allergen exposure, human IgE memory resides in allergen-specific IgG+ memory B cells. These rapidly switch isotype and expand into short-lived IgE+ plasmablasts and serve as a potential target for therapeutic intervention.
All Author:
IlkaHoofPhDaVeroniqueSchultenPhDbJanice A.LayhadiPhDcThomasStranzlPhDaLars H.ChristensenPhDaSara Herrerade la MataPhDbGrégorySeumoisPhDbPanduranganVijayanandPhDbClausLundegaardPhDaKristofferNissPhDaAndersLundM.Sc.aJohanneAhrenfeldtPhDaJensHolmPhDaEstherStevelingMD. PhDcHanisahSharifMSccStephen R.DurhamMD, FRCPcBjörnPetersPhDbMohamed H.ShamjiPhD
　　创建过敏性疾病的科研、科普知识交流平台，为过敏患者提供专业诊断、治疗、预防的共享平台。