Sethi Maya K, Thol Felicitas, Stadler Michael, Heuser Michael, Ganser Arnold, Koenecke Christian, Pabst Oliver
Institute of Immunology, Hannover Medical School, Hannover, Germany.
German Centre for Infection Research (DZIF), partner site Hannover-Braunschweig, Hannover, Germany.
PLoS One. 2017 Jan 17;12(1):e0168096. doi: 10.1371/journal.pone.0168096. eCollection 2017.
After allogeneic hematopoietic stem cell transplantation (HSCT), recovery of humoral immunity is essential to protect from life-threatening infections. However, monitoring the humoral immune system after transplantation with standard techniques in the clinical routine is imprecise. Here, we performed sequencing of mononuclear bone marrow cells to characterize the VH1-repertoire of switched B cells of healthy volunteers and patients undergoing HSCT. Analysis of healthy bone marrow donors and patients showed virtually no clonally related sequences between individuals. Interestingly, clonally related sequences were present in pre- and post-transplantation bone marrow of patients undergoing HSCT for acute myeloid leukemia treatment. We consistently observed such related B cell clones, irrespective of conditioning regimen, donor source or time post transplantation. In general, repertoire diversity was lower in post-HSCT as compared to pre-HSCT samples. However, post-HSCT repertoires retained highly mutated sequences, despite immunosuppressive therapy and presence of T cell deficiency after HSCT. These observations identify key properties of the recovering B cell compartment and provide a conceptual framework for the surveillance of humoral immunity after allogeneic transplantation.
异基因造血干细胞移植（HSCT）后，体液免疫的恢复对于预防危及生命的感染至关重要。然而，在临床常规中使用标准技术监测移植后的体液免疫系统并不精确。在此，我们对单核骨髓细胞进行测序，以表征健康志愿者和接受HSCT的患者转换B细胞的VH1库。对健康骨髓供体和患者的分析显示，个体之间几乎没有克隆相关序列。有趣的是，在接受急性髓系白血病治疗的HSCT患者的移植前和移植后骨髓中存在克隆相关序列。无论预处理方案、供体来源或移植后时间如何，我们始终观察到此类相关B细胞克隆。一般来说，与HSCT前样本相比，HSCT后库的多样性较低。然而，尽管进行了免疫抑制治疗且HSCT后存在T细胞缺陷，但HSCT后的库保留了高度突变的序列。这些观察结果确定了恢复中的B细胞区室的关键特性，并为异基因移植后体液免疫的监测提供了概念框架。
