Donor-derived regulatory B cells are important for suppression of murine sclerodermatous chronic graft-versus-host disease
Donor-derived regulatory B cells are important for suppression of murine sclerodermatous chronic graft-versus-host disease
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DOI：
10.1182/blood-2012-11-465658
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发表时间：
2013-04-18
期刊：
影响因子：
20.3
通讯作者：
Fujimoto, Manabu
中科院分区：
文献类型：
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作者：
Doanh Le Huu;Matsushita, Takashi;Fujimoto, Manabu
慢性移植物抗宿主病(CGVHD)是异基因造血干细胞移植发病率和死亡率的一个日益常见的原因。硬皮瘤性cGVHD(scl-cGVHD)的特点是纤维化和自身免疫特征类似于系统性硬化症(SSC)。将B10.D2骨髓和脾细胞移植到受照射的BALB/c小鼠体内是一种已建立的人SCL-cGVHD模型。为探讨B细胞在SCL-cGVHD中的作用，以CD19缺陷(CD19(-/-))小鼠为供体或受体。CD19(-/-)供者较野生型供者诱发更严重的SCL-cGVHD，但CD19(-/-)受体与野生型受体相比差异无统计学意义。此外，供者B细胞表面CD19缺乏导致早期脾细胞产生IL-6的单核/巨噬细胞、细胞毒性CD8(+)T细胞和Th1细胞的扩张，而在SCL-cGVHD后期T细胞、产生转化生长因子-β的单核/巨噬细胞和Th2细胞在皮肤中的渗透增加。CD19(-/-)供者细胞不能重建产生IL-10的调节性B细胞(B10细胞)，早期过继转移B10细胞可减轻CD19(-/-)供者诱导的SCL-cGVHD的增强表现。因此，供者来源的B10细胞在SCL-cGVHD的发展中具有抑制作用，这为基于调节性B细胞的治疗SCL-cGVHD和SSC的未来研究奠定了基础。
Chronic graft-versus-host disease (cGVHD) is an increasingly frequent cause of morbidity and mortality of allogeneic hematopoietic stem-cell transplantation. Sclerodermatous cGVHD (Scl-cGVHD) is characterized by fibrosis and autoimmune features resembling those of systemic sclerosis (SSc). Transplantation of B10.D2 bone marrow and splenocytes into irradiated BALB/c mice is an established model of human Scl-cGVHD. To examine the role of B cells in Scl-cGVHD, CD19-deficient (CD19(-/-)) mice were used as donors or recipients. CD19(-/-) donors induced more severe Scl-cGVHD than wild-type donors, but use of CD19(-/-) recipients resulted in no significant differences compared with wild-type recipients. Moreover, CD19 deficiency on donor B cells resulted in the expansion of splenic interleukin (IL)-6-producing monocytes/macrophages, cytotoxic CD8(+) T cells, and Th1 cells during the early stage of disease and increased the infiltration of T cells, TGF-beta-producing monocytes/macrophages, and Th2 cells into the skin in the later stage of Scl-cGVHD.IL-10-producing regulatory B cells (B10 cells) were not reconstituted by CD19(-/-) donor cells, and early adoptive transfer of B10 cells attenuated the augmented manifestations of CD19(-/-) donor-induced Scl-cGVHD. Therefore, donor-derived B10 cells have a suppressive role in Scl-cGVHD development, warranting future investigation of regulatory B-cell-based therapy for treatment of Scl-cGVHD and SSc.