Expansion and somatic hypermutation of B-cell clones in rejected human kidney grafts.
Expansion and somatic hypermutation of B-cell clones in rejected human kidney grafts.
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DOI：
10.1097/tp.0000000000000124
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发表时间：
2014-10-15
期刊：
影响因子：
6.2
通讯作者：
Zorn E
中科院分区：
文献类型：
--
作者：
Ferdman J;Porcheray F;Gao B;Moore C;DeVito J;Dougherty S;Thomas MV;Farkash EA;Elias N;Kawai T;Malek SK;Tullius SG;Wong W;Zorn E
B细胞浸润在排斥的同种异体肾移植中很常见，但其组成尚不清楚。本研究的目的是描述排斥的人肾移植物中B细胞浸润的克隆组成。我们采用分子生物学方法对5例移植失败的人肾移植物的部分B细胞进行了鉴定，这些移植物可检测到B细胞浸润。还对一例病例进行了移植物内和血液库之间的比较。在血液和移植物中均观察到冗余序列，尽管移植物的克隆扩增水平显著较高。与血液相比，在移植物中发现的序列中体细胞超突变（SHM）也更常见。与血液序列以及低频率发现的移植物序列中的框架区相比，互补决定区（CDR）中的非沉默突变率显著更高。相比之下，这种优先分布在移植物中以高频率发现的序列中丢失，表明缺乏原位亲和力成熟。最后，在所有检查的样品中，在CD20+浸润中检测不到滤泡树突状细胞。我们在这里提供的证据表明，B细胞克隆扩大，并进行SHM原位。然而，非沉默SHM在高频率移植序列中的均匀分布以及FDC的缺失并不支持浸润性B细胞是功能性生发中心的一部分的观点。
B cell infiltrates are common in rejected kidney allografts, yet their composition is still unclear. The aim of our study was to characterize the clonal composition of B cell infiltrates of rejected human kidney grafts. We used a molecular approach to characterize the partial B cell repertoires of 5 failed human kidney grafts with detectable B cell infiltrates. A comparison between the intragraft and blood repertoire was also conducted for one case. Redundant sequences were observed in both blood and graft, although the level of clonal amplification was significantly higher for the graft. Somatic hypermutations (SHM) were also more frequent in sequences found in the graft compared to the blood. The rate of non-silent mutations was significantly higher in complementarity determining regions (CDR) compared to framework regions in blood sequences as well as in graft sequences found at low frequency. In contrast, this preferential distribution was lost in sequences found at high frequency in the graft, suggesting a lack of affinity maturation in situ. Lastly, follicular dendritic cells were undetectable in CD20+ infiltrates in all samples examined. We provide here evidence that B cell clones expand and undergo SHM in situ. However, the even distribution of non-silent SHM in high frequency graft sequences together with the absence of FDC do not support the view that infiltrating B cells are part of functional germinal centers.