Tolerant Kidney Transplant Patients Produce B Cells with Regulatory Properties
Tolerant Kidney Transplant Patients Produce B Cells with Regulatory Properties
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DOI：
10.1681/asn.2014040404
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发表时间：
2015-10-01
影响因子：
13.6
通讯作者：
Brouard, Sophie
中科院分区：
文献类型：
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作者：
Chesneau, Melanie;Michel, Laure;Brouard, Sophie
尽管B细胞转录谱已被记录为手术耐受的肾移植患者，B细胞在这种耐受中的作用尚未报道。在这项研究中，我们分析了B细胞的作用，从操作耐受患者，健康志愿者，肾移植受者与稳定的移植功能的T细胞抑制。在有或无自体B细胞的情况下，在抗CD 3/抗CD 28刺激后，测量效应CD 4（+）CD 25（-）T细胞的增殖、凋亡和I型促炎细胞因子产生。我们报道了B细胞以剂量依赖性方式抑制CD 4（+）CD 25（-）效应T细胞应答。这种作用需要B细胞与T细胞靶点相互作用，并通过a.颗粒酶B（Gzm B）依赖性途径。耐受性受体具有较高数量的表达Gzm B并显示浆细胞表型的B细胞。最后，Gzm B（+）B细胞的数量依赖于IL-21的产生，而来自耐受受体的B细胞对IL-21（+）T细胞的数量和IL-21的产生都有正调节作用，这表明耐受受体中存在一个反馈回路，该回路增加了过度的B细胞活化并允许调节发生。这些数据提供了对临床耐受性中B细胞介导的免疫调节的表征的见解，并显示了B细胞对来自具有操作耐受性肾移植物的患者的血液中的效应T细胞的潜在调节作用。
Whereas a B cell-transcriptional profile has been recorded for operationally tolerant kidney graft patients, the role that B cells have in this tolerance has not been reported. In this study, we analyzed the role of B cells from operationally tolerant patients, healthy volunteers, and kidney transplant recipients with stable graft function on T cell suppression. Proliferation, apoptosis, and type I proinflammatory cytokine production by effector CD4(+)CD25(-) T cells were measured after anti-CD3/anti-CD28 stimulation with or without autologous B cells. We report that B cells inhibit CD4(+)CD25(-) effector T cell response in a dose-dependent manner. This effect required B cells to interact with T-cell targets and was achieved through a. granzyme B (GzmB)-dependent pathway. Tolerant recipients harbored a higher number of B cells expressing GzmB and displaying a plasma cell phenotype. Finally, GzmB(+) B-cell number was dependent on IL-21 production, and B cells from tolerant recipients but not from other patients positively regulated both the number of IL-21(+) T cells and IL-21 production, suggesting a feedback loop in tolerant recipients that increases excessive B cell activation and allows regulation to take place. These data provide insights into the characterization of B cell-mediated immunoregulation in clinical tolerance and show a potential regulatory effect of B cells on effector T cells in blood from patients with operationally tolerant kidney grafts.