University Department of Pediatrics, DPUO, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital, Rome, Italy.
J Clin Immunol. 2015 May;35(4):373-83. doi: 10.1007/s10875-015-0154-4. Epub 2015 Apr 15.
Hematopoietic cell transplantation (HCT) provides a curative therapy for severe forms of primary immunodeficiencies (PID). While the timing and extent of T-cell reconstitution following transplant for PID has been studied in depth, less is known about the kinetics of B-cell development and long-term restoration of humoral functions, which been often reported to be suboptimal after HCT.
We studied longitudinally B-cell development and function in a cohort of 13 PID patients transplanted between 1997 and 2010, with a follow-up ranging from 0.7 to 15 years. Flow cytometric analysis of naïve and antigen-experienced B-cell subsets and in vitro functional responses to CpG were compared with data from healthy children and correlated with the degree of B-cell chimerism and in vivo antibody production.
We found that total memory B-cells count remained below normal levels for the first 2 years of follow up and progressively normalized. Switched memory B-cells (CD19+CD27+IgD-IgM-) were restored early and better than IgM memory B-cells (CD19+CD27+IgD+IgM+), which remained significantly reduced long-term. The recovery of memory B-cells correlated with good in vivo humoral function and normalization of CpG-response. A complete B-cell reconstitution was usually associated with donor B-cells chimerism and pre-transplant conditioning. Donor source and the underlying genetic defect represented also important variables.
Monitoring of phenotypic and functional changes on B-cells following HCT may prove clinically relevant to tailor patients' care. In particular the analysis of IgM memory and switched memory B-cells in addition to in vitro B-cells stimulation are recommended before Ig replacement therapy (IgRT) discontinuation.
造血细胞移植（HCT）为原发性免疫缺陷（PID）的严重形式提供了一种治愈性治疗方法。虽然 PID 患者移植后 T 细胞重建的时机和程度已经进行了深入研究，但对于 B 细胞发育和体液功能的长期恢复知之甚少，HCT 后这些功能往往恢复不佳。
我们对 1997 年至 2010 年间移植的 13 名 PID 患者进行了队列研究，纵向研究 B 细胞的发育和功能，随访时间为 0.7 至 15 年。通过流式细胞术分析幼稚和抗原经验 B 细胞亚群以及对 CpG 的体外功能反应，并与健康儿童的数据进行比较，并与 B 细胞嵌合程度和体内抗体产生相关。
我们发现，总记忆 B 细胞计数在随访的前 2 年内仍低于正常水平，并逐渐正常化。转换记忆 B 细胞（CD19+CD27+IgD-IgM-）早期恢复且优于 IgM 记忆 B 细胞（CD19+CD27+IgD+IgM+），长期仍显著减少。记忆 B 细胞的恢复与良好的体内体液功能和 CpG 反应的正常化相关。完全的 B 细胞重建通常与供者 B 细胞嵌合和移植前预处理相关。供体来源和潜在的遗传缺陷也是重要的变量。
监测 HCT 后 B 细胞的表型和功能变化可能对患者的护理具有临床相关性。特别是在停止 Ig 替代治疗（IgRT）之前，建议分析 IgM 记忆和转换记忆 B 细胞以及体外 B 细胞刺激。
