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.

中文翻译：

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人类心脏同种异体移植血管病变中免疫浸润中的 B 细胞克隆扩增。

心脏同种异体移植物血管病变 (CAV) 与移植物内 B 细胞浸润有关。在这里，我们使用 4 个带有 CAV 的移植标本研究了 B 细胞浸润的克隆组成。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。结果显示移植物中的 B 细胞克隆扩增强劲，但并非所有病例都在血液中。在移植物的不同位置检测到几个扩增的 B 细胞克隆，其特征是其独特重排的互补决定区 3。与血 B 细胞相比，移植物内 B 细胞的序列也显示移植物中突变重排水平升高。移植物中每次重排的体细胞突变数量也高于血液中的数量，这表明 B 细胞继续在原位成熟。总体，我们的研究证明了 B 细胞在 CAV 人类心脏同种异体移植物中的克隆扩增。这种局部 B 细胞反应可能通过需要确定的机制促进 CAV 的病理生理学。