Xing Chen, Ma Ning, Xiao He, Wang Xiaoqian, Zheng Mingke, Han Gencheng, Chen Guojiang, Hou Chunmei, Shen Beifen, Li Yan, Wang Renxi
*Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
*Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China; Department of Rheumatology, First Hospital of Jilin University, Changchun, China; Department of Immunology, Medical College of Henan University, Kaifeng, China; and State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China
J Leukoc Biol. 2015 Mar;97(3):547-56. doi: 10.1189/jlb.3A0414-213RR. Epub 2014 Dec 16.
This study tested the hypothesis that besides the spleen, LNs, peripheral blood, and thymus contain a regulatory IL-10-producing CD19(+)CD5(+)CD1d(high) B cell subset that may play a critical role in the maintenance of immune homeostasis. Indeed, this population was identified in the murine thymus, and furthermore, when cocultured with CD4(+) T cells, this population of B cells supported the maintenance of CD4(+)Foxp3(+) Tregs in vitro, in part, via the CD5-CD72 interaction. Mice homozygous for Cd19(Cre) (CD19(-/-)) express B cells with impaired signaling and humoral responses. Strikingly, CD19(-/-) mice produce fewer CD4(+)Foxp3(+) Tregs and a greater percentage of CD4(+)CD8(-) and CD4(-)CD8(+) T cells. Consistent with these results, transfer of thymic CD19(+)CD5(+)CD1d(hi) B cells into CD19(-/-) mice resulted in significantly up-regulated numbers of CD4(+)Foxp3(+) Tregs with a concomitant reduction in CD4(+)CD8(-) and CD4(-)CD8(+) T cell populations in the thymus, spleen, and LNs but not in the BM of recipient mice. In addition, thymic CD19(+)CD5(+)CD1d(hi) B cells significantly suppressed autoimmune responses in lupus-like mice via up-regulation of CD4(+)Foxp3(+) Tregs and IL-10-producing Bregs. This study suggests that thymic CD19(+)CD5(+)CD1d(hi)IL-10(+) Bregs play a critical role in the maintenance of immune homeostasis.
除脾脏、淋巴结、外周血和胸腺外，还存在一个产生调节性白细胞介素-10的CD19(+)CD5(+)CD1d(高)B细胞亚群，其可能在维持免疫稳态中发挥关键作用。实际上，在小鼠胸腺中鉴定出了这一细胞群，此外，当与CD4(+)T细胞共培养时，这群B细胞部分通过CD5 - CD72相互作用在体外支持CD4(+)Foxp3(+)调节性T细胞的维持。Cd19(Cre)纯合子小鼠(CD19(-/-))表达信号传导和体液反应受损的B细胞。令人惊讶的是，CD19(-/-)小鼠产生的CD4(+)Foxp3(+)调节性T细胞较少，而CD4(+)CD8(-)和CD4(-)CD8(+)T细胞的比例更高。与这些结果一致，将胸腺CD19(+)CD5(+)CD1d(高)B细胞转移到CD19(-/-)小鼠体内，导致受体小鼠胸腺、脾脏和淋巴结中CD4(+)Foxp3(+)调节性T细胞数量显著上调，同时CD4(+)CD8(-)和CD4(-)CD8(+)T细胞群体减少，但骨髓中没有。此外，胸腺CD19(+)CD5(+)CD1d(高)B细胞通过上调CD4(+)Foxp3(+)调节性T细胞和产生白细胞介素-10的调节性B细胞，显著抑制了狼疮样小鼠的自身免疫反应。本研究表明，胸腺CD19(+)CD5(+)CD1d(高)IL-10(+)调节性B细胞在维持免疫稳态中发挥关键作用。
