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循环自动反应性前等离子细胞的生成由天真B细胞在乳病中提供燃料

Ida Lindeman¹, Lene S Høydahl¹, Asbjørn Christophersen¹

¹Norwegian Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital - Rikshospitalet, Oslo, Norway.

|April 5, 2024

概括

在乳病 (CeD) 中,在血液中发现了针对转谷氨酶2 (TG2) 的特定的IgA生成B细胞. 这些细胞与其他IgA细胞不同,表明CeD中自反应性B细胞生成的独特途径.

科学领域:

免疫学免疫学免疫学
胃肠病学胃肠病学
这是一种自身免疫力.

背景情况:

对转谷氨酸酶2 (TG2) 的自身抗体是乳病 (CeD) 的标志.
在CeD患者的肠道活检中,TG2特异性免疫球蛋白 (Ig) A等离子细胞普遍存在.

研究的目的:

鉴定CeD患者血液中自反应性B细胞的种群特征.
为了研究循环TG2特异性IgA产生B细胞的起源和特性.

主要方法:

在未经治疗的CeD患者和对照人群中分析循环TG2特异性IgA细胞.
血液和肠道血细胞之间的克隆关系评估.
现型特征包括CD27,IgD和可变区域突变分析.
识别肠道归宿分子和T细胞参与.

主要成果:

在未经治疗的CeD患者中检测到循环的TG2特异性IgA细胞,但在对照组中没有.
这些细胞表现出与肠道等离子细胞的克隆相关性,并表达了肠道归属分子.
特定于TG2的IgA细胞是CD27阴性 (双阴性IgD^-CD27^-),并且比其他IgA细胞更少的突变.
这些细胞表现出血细胞或激活的记忆B细胞表型.

结论:

在CeD中循环的TG2特异性IgA细胞很可能是血细胞前体.
这些自身反应性IgA细胞可以通过长期招募原始B细胞来产生.
一个涉及质特异性CD4+T细胞的额外毛囊反应似乎驱动了CeD中自身反应性IgA细胞的产生.

关键词:

B 细胞 B 细胞 B 细胞 CD27 CD27 CD27 CD27 CD27 CD27 CD27 CD27 CD27 CD27 CD27 CD27 CD27 CP: 免疫学免疫学在 IgA A 里面.抗体是对抗体的重要组成部分.这是自身免疫力.患有乳性疾病的患者.粘膜免疫学粘膜免疫学血细胞是血细胞的组成部分.

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