原標(biāo)題：過敏原特異性IgG+記憶B細(xì)胞與IgE記憶應(yīng)答短暫相關(guān)
　　①人體中的IgE在所有免疫球蛋白中含量最少，受到嚴(yán)格的調(diào)控，產(chǎn)生IgE的B細(xì)胞較少。IgE應(yīng)答的細(xì)胞起源和進(jìn)化目前尚不清楚。②目的：探討通過舌下免疫治療(SLIT)，黏膜受到過敏原刺激后，IgE記憶應(yīng)答的細(xì)胞和克隆來源。③在一項(xiàng)隨機(jī)雙盲、安慰劑對(duì)照、時(shí)程SLIT（舌下免疫治療）研究中，分別在基線、4周、8周、16周、28周和52周時(shí)，采集40名季節(jié)性過敏性鼻炎患者的外周血單核細(xì)胞(PBMCs)和鼻活組織切片，從外周血單核細(xì)胞中提取RNA，分選B細(xì)胞和鼻活組織切片進(jìn)行VH測(cè)序。此外，單克隆抗體來源于單一的B細(xì)胞轉(zhuǎn)錄組。④結(jié)合VH測(cè)序和單細(xì)胞轉(zhuǎn)錄組學(xué)發(fā)現(xiàn)了直接證據(jù)，證明了存活短暫的IgE+漿母細(xì)胞和IgG+記憶B細(xì)胞(稱為IgGE)的兩個(gè)同源且功能相關(guān)的B細(xì)胞亞群的平行增加。通過SLIT，粘膜草花粉過敏原暴露導(dǎo)致IgE和IgGE序列高度多樣化。根據(jù)重鏈同型、體細(xì)胞超突變和克隆組成，這些基因發(fā)生了廣泛的突變，并表現(xiàn)出相對(duì)的穩(wěn)定性。單個(gè)IgGE +記憶B細(xì)胞和IgE+ 前漿母細(xì)胞轉(zhuǎn)錄組編碼的抗體是針對(duì)主要草花粉過敏原的，能夠在極低的過敏原濃度下誘導(dǎo)嗜堿性粒細(xì)胞活化。⑤我們首次發(fā)現(xiàn)，在粘膜暴露于過敏原時(shí)，人的IgE記憶存在于過敏原特異性IgG+記憶B細(xì)胞中。這些細(xì)胞快速轉(zhuǎn)換亞型并擴(kuò)展為存活短暫的IgE+ 漿母細(xì)胞，成為治療干預(yù)的潛在靶點(diǎn)。
延伸閱讀
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, FRCPcBj?rnPetersPhDbMohamed H.ShamjiPhD
　　創(chuàng)建過敏性疾病的科研、科普知識(shí)交流平臺(tái)，為過敏患者提供專業(yè)診斷、治療、預(yù)防的共享平臺(tái)。