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抗原特异性免疫疗法调节肠道中的 B 细胞活性。

Antigen-specific immunotherapy regulates B cell activities in the intestine.

机构信息

Department of Geriatrics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.

Department of Orthopedics, First Affiliated Hospital of Chongqing Medical University, Chongqing 40016, China.

出版信息

J Biol Chem. 2013 Jun 7;288(23):16383-16390. doi: 10.1074/jbc.M113.456202. Epub 2013 Apr 15.

Abstract

Mature B cells (BCs) express CD23 and B cell receptors. Whether activation of CD23 and B cell receptors has different effects on BC activities is unclear. This study aims to investigate the mechanism by which the specific antigen immunotherapy regulates the activation of BCs in the skewed Th2 responses. Mice were sensitized to ovalbumin. The specific antigen vaccination (SAV) at graded doses was employed to modulate the activities of BCs in which the expression of IL-10, IgE, matrix metalloproteinase-9 (MMP9), CD23, and serum soluble CD23 by BCs was evaluated. The immune regulatory effect of BCs primed by lower or higher SAV doses was observed with an adoptive transfer mouse experiment. SAV activated CD23 to produce IL-10 in BCs at lower doses. The higher doses of SAV increased the expression of MMP9 in BCs that reduced the amounts of CD23 in BCs and increased the serum levels of soluble CD23, which was abrogated by the pretreatment with MMP9 inhibitor. Adoptively transfer with BCs primed by lower doses of SAV inhibited the ongoing antigen-specific Th2 responses whereas the BCs primed by higher doses of SAV exacerbated the ongoing Th2 responses. Exposure to specific antigens at optimal doses can activate BCs to produce IL-10 to suppress the skewed antigen-specific Th2 responses. The antigen doses of SAV higher than the optimal doses may promote the production of soluble CD23 to exacerbate the ongoing immune responses.

摘要

成熟 B 细胞 (BC) 表达 CD23 和 B 细胞受体。CD23 和 B 细胞受体的激活是否对 BC 活性有不同的影响尚不清楚。本研究旨在探讨特异性抗原免疫治疗调节偏倚 Th2 反应中 BC 激活的机制。用卵清蛋白致敏小鼠。采用分级剂量的特异性抗原疫苗接种 (SAV) 来调节 BC 活性,评估 IL-10、IgE、基质金属蛋白酶-9 (MMP9)、CD23 和血清可溶性 CD23 的表达。通过过继转移小鼠实验观察了低剂量或高剂量 SAV 激活的 BC 的免疫调节作用。SAV 在低剂量下激活 CD23 以在 BC 中产生 IL-10。更高剂量的 SAV 增加了 MMP9 在 BC 中的表达,降低了 BC 中的 CD23 含量,并增加了血清可溶性 CD23 的水平,这被 MMP9 抑制剂预处理所阻断。用低剂量 SAV 预激活的 BC 过继转移抑制了正在进行的抗原特异性 Th2 反应,而用高剂量 SAV 预激活的 BC 加剧了正在进行的 Th2 反应。暴露于最佳剂量的特异性抗原可激活 BC 产生 IL-10 来抑制偏倚的抗原特异性 Th2 反应。高于最佳剂量的 SAV 抗原剂量可能会促进可溶性 CD23 的产生,从而加剧正在进行的免疫反应。

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