Post-transplantation cyclophosphamide restores early B-cell lymphogenesis that suppresses subsequent chronic graft-versus-host disease
Post-transplantation cyclophosphamide restores early B-cell lymphogenesis that suppresses subsequent chronic graft-versus-host disease
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DOI：
10.1038/s41409-020-01100-0
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发表时间：
2020-10-30
影响因子：
4.8
通讯作者：
Matsuoka, Ken-ichi
中科院分区：
文献类型：
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作者：
Iwamoto, Miki;Ikegawa, Shuntaro;Matsuoka, Ken-ichi
近年来，许多研究都将b细胞免疫异常作为异基因造血干细胞移植（HSCT）后慢性移植物抗宿主病（cGVHD）发病的主要因素[1,2]。Sarantopoulos等人首次报道了移植后环境中异常的B细胞稳态，naïve B细胞淋巴减少和过量的B细胞活化因子（BAFF）促进了B细胞对抗原的反应性，提高了活化B细胞的存活率[3,4]。随后的研究表明，滤泡辅助性T细胞（Tfhs）促进了naïve B细胞向生发中心B细胞的分化，这可能导致IgG同种异体抗体的异常产生，导致cgvhd靶器官的组织损伤[5,6]。基于这些发现，针对活化B细胞的治疗方法已被开发用于cGVHD患者[7-10]。然而，可能与移植后早期naïve B淋巴细胞减少相关的因素，可能引发慢性GVHD的基础发病机制尚未得到很好的研究。
In recent years, many studies have focused on the abnormality of B-cell immunity as a major factor in the pathogenesis of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT)[1, 2]. Sarantopoulos et al. firstly reported abnormal B-cell homeostasis in the post-transplant environment where naïve B-cell lymphopenia and excessive B-cell activation factor (BAFF) promoted the responsiveness of B cells to antigens, and increased survival of activated B cells [3, 4]. Ensuing studies demonstrated that follicular helper T cells (Tfhs) promoted the differentiation from naïve B cells into germinal center B cells, which may result in the aberrant production of IgG alloantibodies causing tissue damage in cGVHD-target organs [5, 6]. Based on these findings, therapies targeting activated B cells have been developed for patients with cGVHD [7–10]. However, the factors that may be associated with naïve B lymphopenia early after transplant, which could trigger to form the basal pathogenesis of chronic GVHD, have not been well studied.