Autoreactive IgG and IgA B Cells Evolve through Distinct Subclass Switch Pathways in the Autoimmune Disease Pemphigus Vulgaris.
Autoreactive IgG and IgA B Cells Evolve through Distinct Subclass Switch Pathways in the Autoimmune Disease Pemphigus Vulgaris.
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DOI：
10.1016/j.celrep.2018.07.093
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发表时间：
2018-08-28
期刊：
影响因子：
8.8
通讯作者：
Payne AS
中科院分区：
文献类型：
--
作者：
Ellebrecht CT;Mukherjee EM;Zheng Q;Choi EJ;Reddy SG;Mao X;Payne AS
自身反应性B细胞的谱系分析可以揭示自身免疫的起源。在自身免疫性疾病寻常型天疱疮（PV）中，桥粒芯糖蛋白3（DSG 3）和DSG 1自身抗体主要是IgG 4亚类，而IgG 1和伊加亚类的频率较低，这促使我们研究抗DSG IgG 4 B细胞是否与IgG 1、IgA 1和IgA 2共享谱系。将亚型特异性B细胞深度测序与高通量抗体筛选相结合，我们从4名PV患者中鉴定了80种DSG反应性谱系。大多数抗DSG IgG 4 B细胞与其他亚类缺乏克隆关系，并优先靶向DSG粘附结构域，而抗DSG伊加经常从其他亚类进化而来或进化至其他亚类，并识别更广泛的表位。我们的研究结果表明，抗DSG IgG 4 B细胞主要独立发展或从其他亚类分化早期，伊加是最常见的不是在PV的IgG自身反应性的起源。这些数据提供了对自身反应性如何在B细胞亚类中多样化的见解。Ellebrecht等人使用下一代测序来鉴定自身免疫性疾病寻常天疱疮中抗原特异性B细胞之间的克隆关系。他们发现，自身反应性IgG 4 B细胞在很大程度上与自身反应性IgG 1和伊加在克隆上不同，从而阐明了使人类自身免疫反应多样化和改变的类别转换途径。
Lineage analysis of autoreactive B cells can reveal the origins of autoimmunity. In the autoimmune disease pemphigus vulgaris (PV), desmoglein 3 (DSG3) and DSG1 autoantibodies are predominantly of the IgG4 subclass and less frequently of IgG1 and IgA subclasses, prompting us to investigate whether anti-DSG IgG4 B cells share lineages with IgG1, IgA1, and IgA2. Combining subclass-specific B cell deep sequencing with high-throughput antibody screening, we identified 80 DSG-reactive lineages from 4 PV patients. Most anti-DSG IgG4 B cells lacked clonal relationships to other subclasses and preferentially targeted DSG adhesion domains, whereas anti-DSG IgA frequently evolved from or to other subclasses and recognized a broader range of epitopes. Our findings suggest that anti-DSG IgG4 B cells predominantly evolve independently or diverge early from other subclasses and that IgA is most often not the origin of IgG autoreactivity in PV. These data provide insight into how autoreactivity diversifies across B cell subclasses. Ellebrecht et al. use next-generation sequencing to identify clonal relationships among antigen-specific B cells in the autoimmune disease pemphigus vulgaris. They find that autoreactive IgG4 B cells are largely clonally distinct from autoreactive IgG1 and IgA, thus elucidating the class-switch pathways that diversify and modify an autoimmune response in humans.
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影响因子：
3.8
作者：
Cho, Michael Jeffrey;Ellebrecht, Christoph T.;Payne, Aimee S.
通讯作者：
Payne, Aimee S.
影响因子：
7.7
作者：
Horns, Felix;Vollmers, Christopher;Quake, Stephen R.
通讯作者：
Quake, Stephen R.
影响因子：
3.4
作者：
BHOL, K;MOHIMEN, A;AHMED, AR
通讯作者：
AHMED, AR
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
影响因子：
2.7
作者：
Chiu, Chun-Huo;Chao, Anne
通讯作者：
Chao, Anne