B cell clonal expansion within immune infiltrates in human cardiac allograft vasculopathy
B cell clonal expansion within immune infiltrates in human cardiac allograft vasculopathy
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DOI：
10.1111/ajt.15737
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发表时间：
2019-12-27
影响因子：
8.8
通讯作者：
Zorn, Emmanuel
中科院分区：
文献类型：
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作者：
Moore, Carolina;Gao, Baoshan;Zorn, Emmanuel
心脏移植物血管病（CAV）与移植物内B细胞浸润有关。在这里，我们研究了克隆组成的B细胞浸润使用4移植标本与CAV。使用深度测序，我们分析了移植物和血液中的免疫球蛋白重链可变区库。结果显示，所有病例的移植物中均存在强大的B细胞克隆扩增，但血液中没有。在移植物的不同位置检测到几个扩增的B细胞克隆，其特征在于其独特的重排互补决定区3。与血液B细胞相比，移植物内B细胞的序列也显示出移植物中突变重排水平升高。每次重排的体细胞突变数量在移植物中也高于血液中，表明B细胞在原位继续成熟。总的来说，我们的研究表明，B细胞克隆性扩增的人心脏移植与CAV。这种局部B细胞反应可能通过一种需要确定的机制参与CAV的病理生理学。
Cardiac allograft vasculopathy (CAV) is associated with intragraft B cell infiltrates. Here, we studied the clonal composition of B cell infiltrates using 4 graft specimens with CAV. Using deep sequencing, we analyzed the immunoglobulin heavy chain variable region repertoire in both graft and blood. Results showed robust B cell clonal expansion in the graft but not in the blood for all cases. Several expanded B cell clones, characterized by their uniquely rearranged complementarity-determining region 3, were detected in different locations in the graft. Sequences from intragraft B cells also showed elevated levels of mutated rearrangements in the graft compared to blood B cells. The number of somatic mutations per rearrangement was also higher in the graft than in the blood, suggesting that B cells continued maturing in situ. Overall, our studies demonstrated B cell clonal expansion in human cardiac allografts with CAV. This local B cell response may contribute to the pathophysiology of CAV through a mechanism that needs to be identified.