Allergen-specific IgG(+) memory B cells are temporally linked to IgE memory responses.
Allergen-specific IgG(+) memory B cells are temporally linked to IgE memory responses.
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过敏原特异性IgG（+）内存B细胞在时间上链接到IgE内存响应。
DOI：
10.1016/j.jaci.2019.11.046
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发表时间：
2020-07
期刊：
影响因子：
--
通讯作者：
Andersen PS
中科院分区：
文献类型：
--
作者：
Hoof I;Schulten V;Layhadi JA;Stranzl T;Christensen LH;Herrera de la Mata S;Seumois G;Vijayanand P;Lundegaard C;Niss K;Lund A;Ahrenfeldt J;Holm J;Steveling E;Sharif H;Durham SR;Peters B;Shamji MH;Andersen PS
IgE是最不丰富的免疫球蛋白，并且受到严格的调控，并且产生IgE的B细胞是罕见的。IgE反应的细胞起源和演变知之甚少。通过舌下免疫疗法（SLIT）研究了粘膜变应原暴露后IgE记忆反应的细胞和克隆起源。在一项随机、双盲、安慰剂对照、时程SLIT研究中，在基线和第4、8、16、28和52周时从40名季节性变应性鼻炎成人中收集PBMC和鼻活检样本。从PBMC、分选的B细胞和鼻活检样品中提取RNA用于重链可变基因库测序。此外，mAb来源于单个B细胞转录组。结合重链可变基因库测序和单细胞转录组学，得到了2种克隆和功能相关的B细胞亚群（短寿命IgE+浆母细胞和IgG+记忆B细胞）平行加强的直接证据。通过SLIT暴露于粘膜草花粉过敏原导致了高度多样化的IgE和IgGE谱系。根据重链同种型、体细胞超突变和克隆组成，这些基因广泛突变，并且表现出相对稳定。单个IgGE+记忆B细胞和IgE+ preplasmablast转录组编码的抗体是特异性的主要草花粉过敏原，并能够在非常低的过敏原浓度引起嗜碱性粒细胞活化。我们首次发现，在粘膜变应原暴露时，人IgE记忆存在于变应原特异性IgG+记忆B细胞中。这些细胞迅速转换同种型，扩增成短寿命的IgE+浆母细胞，并作为治疗干预的潜在靶点。
IgE is the least abundant immunoglobulin and tightly regulated, and IgE-producing B cells are rare. The cellular origin and evolution of IgE responses are poorly understood. The cellular and clonal origin of IgE memory responses following mucosal allergen exposure by sublingual immunotherapy (SLIT) were investigated. In a randomized double-blind, placebo-controlled, time course SLIT study, PBMCs and nasal biopsy samples were collected from 40 adults with seasonal allergic rhinitis at baseline and at 4, 8, 16, 28, and 52 weeks. RNA was extracted from PBMCs, sorted B cells, and nasal biopsy samples for heavy chain variable gene repertoire sequencing. Moreover, mAbs were derived from single B-cell transcriptomes. Combining heavy chain variable gene repertoire sequencing and single-cell transcriptomics yielded direct evidence of a parallel boost of 2 clonally and functionally related B-cell subsets of short-lived IgE+ plasmablasts and IgG+ memory B cells. Mucosal grass pollen allergen exposure by SLIT resulted in highly diverse IgE and IgGE repertoires. These were extensively mutated and appeared relatively stable as per heavy chain isotype, somatic hypermutations, and clonal composition. Single IgGE+ memory B-cell and IgE+ preplasmablast transcriptomes encoded antibodies that were specific for major grass pollen allergens and able to elicit basophil activation at very low allergen concentrations. For the first time, we have shown that on mucosal allergen exposure, human IgE memory resides in allergen specific IgG+ memory B cells. These cells rapidly switch isotype, expand into short-lived IgE+ plasmablasts, and serve as a potential target for therapeutic intervention.
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表达人IgE的B细胞和浆细胞的个体发育。
影响因子：
12.4
作者：
Ramadani F;Bowen H;Upton N;Hobson PS;Chan YC;Chen JB;Chang TW;McDonnell JM;Sutton BJ;Fear DJ;Gould HJ
通讯作者：
Gould HJ
影响因子：
14.2
作者：
James, Louisa K.;Shamji, Mohamed H.;Durham, Stephen R.
通讯作者：
Durham, Stephen R.
影响因子：
32.4
作者：
Erazo, Agustin;Kutchukhidze, Nino;Lafaille, Juan J.
通讯作者：
Lafaille, Juan J.
影响因子：
14.2
作者：
Berkowska, Magdalena A.;Heeringa, Jorn J.;van Zelm, Menno C.
通讯作者：
van Zelm, Menno C.
DOI：
10.1016/j.jaci.2015.05.029
发表时间：
2016-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Hoh RA;Joshi SA;Liu Y;Wang C;Roskin KM;Lee JY;Pham T;Looney TJ;Jackson KJL;Dixit VP;King J;Lyu SC;Jenks J;Hamilton RG;Nadeau KC;Boyd SD
通讯作者：
Boyd SD