Local Clonal Diversification and Dissemination of B Lymphocytes in the Human Bronchial Mucosa.
Local Clonal Diversification and Dissemination of B Lymphocytes in the Human Bronchial Mucosa.
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DOI：
10.3389/fimmu.2018.01976
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发表时间：
2018
影响因子：
7.3
通讯作者：
Kleinstein SH
中科院分区：
文献类型：
--
作者：
Ohm-Laursen L;Meng H;Chen J;Zhou JQ;Corrigan CJ;Gould HJ;Kleinstein SH
适应性体液免疫反应的有效性可能需要在整个身体中产生多样化但集中的区域B细胞抗体。在此，我们首次研究支气管粘膜中的B细胞库，这是从大气中吸入抗原的重要屏障。为了实现这一目标，我们应用高通量适应性免疫受体库测序（AIRR-Seq）对来自哮喘患者和健康受试者右肺四个不同部位的10个支气管活检进行了分析。虽然大多数已鉴定的B细胞克隆仅限于单个位点，但许多克隆在多个位点播散。克隆成员在邻近活检组织之间比在远端活检组织之间共享更多，这表明局部粘膜迁移和/或B细胞通过血液或淋巴的归巢机制。一小部分克隆跨越支气管粘膜和外周血，表明这些隔室之间正在进行贩运。哮喘患者的支气管粘膜B细胞库在地理上变化更大，但与健康受试者相比多样性更少，这表明在特应性哮喘中存在持续的抗原驱动的体液免疫反应。这是特应性的特征还是疾病状态，还有待于进一步的研究。我们在支气管粘膜观察到一个高度突变和抗原选择的igd细胞亚群。在哮喘个体中发现这些细胞的丰度相对较高，但在健康受试者中也发现，尽管丰度较低。这一新颖的发现值得在更大规模的研究对象中进行进一步的探索。
The efficacy of the adaptive humoral immune response likely requires diverse, yet focused regional B cell antibody production throughout the body. Here we address, in the first study of its kind, the B cell repertoire in the bronchial mucosa, an important barrier to antigens inhaled from the atmosphere. To accomplish this, we have applied high-throughput Adaptive Immune Receptor Repertoire Sequencing (AIRR-Seq) to 10 bronchial biopsies from altogether four different sites in the right lungs from an asthmatic patient and a healthy subject. While the majority of identified B cell clones were restricted to a single site, many were disseminated in multiple sites. Members of a clone were shared more between adjacent biopsies than between distal biopsies, suggesting local mucosal migration and/or a homing mechanism for B cells through the blood or lymph. A smaller fraction of clones spanned the bronchial mucosa and peripheral blood, suggesting ongoing trafficking between these compartments. The bronchial mucosal B cell repertoire in the asthmatic patient was geographically more variable but less diverse compared to that of the healthy subject, suggesting an ongoing, antigen-driven humoral immune response in atopic asthma. Whether this is a feature of atopy or disease status remains to be clarified in future studies. We observed a subset of highly mutated and antigen-selected IgD-only cells in the bronchial mucosa. These cells were found in relative high abundance in the asthmatic individual but also, albeit at lower abundance, in the healthy subject. This novel finding merits further exploration using a larger cohort of subjects.
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