Ontogeny of human IgE-expressing B cells and plasma cells.
Ontogeny of human IgE-expressing B cells and plasma cells.
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表达人IgE的B细胞和浆细胞的个体发育。
作者：
Ramadani F;Bowen H;Upton N;Hobson PS;Chan YC;Chen JB;Chang TW;McDonnell JM;Sutton BJ;Fear DJ;Gould HJ
表达IgE（IgE+）的浆细胞（PC）提供了过敏原特异性IgE的连续来源，这是过敏反应的核心。IgE+细胞在体内的极度稀疏使他们的研究几乎完全局限于小鼠模型。表征人IgE+ PC的发育途径并确定人IgE+ PC的个体发生。为了产生人IgE+细胞，我们用IL-4和抗-CD 40培养扁桃体B细胞。使用FACS和RT-PCR，我们检查了产生的IgE+细胞的表型，扁桃体B-细胞亚群产生IgE+ PC的能力以及涉及的类别转换途径。我们已经确定了IgE+ PC发育途径的三个表型阶段，即（i）IgE+生发中心（GC）样B细胞，（ii）IgE+ PC样“浆母细胞”和（iii）IgE+ PC。对于IgG 1+细胞也观察到相同的表型阶段。总扁桃体B细胞通过直接和顺序转换产生IgE+ PC，而分离的GC B-细胞部分（IgE+ PC的主要来源）通过顺序转换产生IgE+ PC。IgE+细胞的PC分化伴随着与小鼠mIgE同源的短型膜IgE（mIgES）的表面表达下调和长型mIgE（mIgEL）的上调，其与增强的B-细胞存活相关，并在人体中表达，但在小鼠中不表达。从扁桃体GC B细胞产生IgE+ PC主要通过从IgG的顺序转换发生。mIgEL/mIgES比值可能与PC分化和过敏性疾病期间IgE+ B细胞的存活有关。
IgE‐expressing (IgE+) plasma cells (PCs) provide a continuous source of allergen‐specific IgE that is central to allergic responses. The extreme sparsity of IgE+ cells in vivo has confined their study almost entirely to mouse models. To characterize the development pathway of human IgE+ PCs and to determine the ontogeny of human IgE+ PCs. To generate human IgE+ cells, we cultured tonsil B cells with IL‐4 and anti‐CD40. Using FACS and RT‐PCR, we examined the phenotype of generated IgE+ cells, the capacity of tonsil B‐cell subsets to generate IgE+ PCs and the class switching pathways involved. We have identified three phenotypic stages of IgE+ PC development pathway, namely (i) IgE+germinal centre (GC)‐like B cells, (ii) IgE+ PC‐like ‘plasmablasts’ and (iii) IgE+ PCs. The same phenotypic stages were also observed for IgG1+ cells. Total tonsil B cells give rise to IgE+ PCs by direct and sequential switching, whereas the isolated GC B‐cell fraction, the main source of IgE+ PCs, generates IgE+ PCs by sequential switching. PC differentiation of IgE+ cells is accompanied by the down‐regulation of surface expression of the short form of membrane IgE (mIgES), which is homologous to mouse mIgE, and the up‐regulation of the long form of mIgE (mIgEL), which is associated with an enhanced B‐cell survival and expressed in humans, but not in mice. Generation of IgE+ PCs from tonsil GC B cells occurs mainly via sequential switching from IgG. The mIgEL/mIgES ratio may be implicated in survival of IgE+ B cells during PC differentiation and allergic disease.
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影响因子：
2.2
作者：
Iglesias-Ussel, Maria;Marchionni, Luigi;Romerio, Fabio
通讯作者：
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影响因子：
32.4
作者：
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影响因子：
14.2
作者：
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通讯作者：
Lambrecht, Bart N.
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.
影响因子：
4.4
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通讯作者：
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