Diversity of B Cell Populations and Ig Repertoire in Human Lungs.

Diversity of B Cell Populations and Ig Repertoire in Human Lungs.
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DOI:
10.4049/jimmunol.2200340
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发表时间:
2023-08-01
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Kepler TB
Kepler TB
中科院分区:
其他
文献类型:
--
作者:
Aihara F;Wang Y;Belkina AC;Fearns R;Mizgerd JP;Feng F;Kepler TB

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人类肺部携带着一种独特的微生物组,适应充满空气的粘液环境,这种环境的存在需要免疫系统能够识别有害人群,同时防止对细菌的反应。肺中的B细胞在肺免疫中起关键作用,产生抗原特异性抗体以及用于免疫活化和调节的细胞因子分泌。在这里,我们通过分析患者配对的肺和血液样本,比较了人肺中的B细胞亚群与循环细胞。我们发现,相对于血液,肺中的CD 19+、CD 20 + B细胞池显著较小。CD 27+、IgD−、类别转换记忆B细胞(CS Bcells)在肺B细胞库中占较大比例。肺中的驻留标记物CD69也显著较高。我们还测序了CS BAE的免疫球蛋白可变区基因(IgVRG),这些基因表达或不表达CD69。我们观察到肺结核的IgVRG与循环中的IgVRG一样,从未突变的共同祖先(UCA)发生严重突变。此外,我们发现准克隆内的后代可以获得或失去CD69表达,无论亲本克隆是否表达驻留标记。总的来说,我们的研究结果表明,尽管其血管化的性质,人类肺部携带独特比例的B细胞亚群。肺结核的IgVRGs与血液中的IgVRGs一样多样,并且肺结核的后代保留获得或失去居留权的能力。
The human lung carries a unique microbiome adapted to the air-filled, mucus-lined environment, the presence of which requires an immune system capable of recognizing harmful populations while preventing reactions towards commensals. B cells in the lung play a key role in pulmonary immunity, generating antigen specific antibodies as well as cytokine secretion for immune activation and regulation. Here we compared B cell subsets in human lungs versus circulating cells by analyzing patient-paired lung and blood samples. We found a significantly smaller pool of CD19+, CD20+ B cells in the lung relative to the blood. CD27+, IgD−, class-switched memory B cells (CS Bmem) composed a larger proportion of the pool of pulmonary B cells. The residency marker CD69 was also significantly higher in the lung. We also sequenced the immunoglobulin variable region genes (IgVRGs) of CS Bmem that do, or do not, express CD69. We observed the IgVRGs of pulmonary Bmem to be as heavily mutated from the unmutated common ancestor (UCA) as those in circulation. Furthermore, we found progeny within a quasi-clone can gain or lose CD69 expression, regardless of whether the parent clone expressed the residency marker or not. Overall, our results show that despite its vascularized nature, human lungs carry a unique proportion of B cell subsets. The IgVRGs of pulmonary Bmems are as diverse as those in blood, and progeny of Bmems retain the ability to gain or lose residency.
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