Peripheral CD27-CD21- B-cells represent an exhausted lymphocyte population in hepatitis C cirrhosis

Peripheral CD27-CD21- B-cells represent an exhausted lymphocyte population in hepatitis C cirrhosis
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DOI:
10.1016/j.clim.2013.12.001
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发表时间:
2014-02-01
影响因子:
8.6
通讯作者:
Kaplan, David E.
Kaplan, David E.
中科院分区:
医学3区
文献类型:
--
作者:
Doi, Hiroyoshi;Tanoue, Shiroh;Kaplan, David E.

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丙型肝炎肝硬化与记忆B细胞的彻底消失有关。我们试图确定这种丢失是否与具有B细胞耗竭特征的CD 27(-)CD 21(-)组织样记忆B细胞的扩增有关。为此,我们定量了健康、非丙型肝炎病毒感染和丙型肝炎患者中CD 27(-)CD 21(-)B细胞的频率。我们研究了假定的抑制性受体的表达,CD 27/CD 21定义的B细胞亚群在B细胞受体和/或CD 40刺激后的增殖和免疫球蛋白分泌能力。我们发现,在HCV感染患者中,相对于健康供体,CD 27(-)CD 21(-)B细胞的频率显著增加。在激动性刺激后,CD 2(-)CD 21(-)B细胞相对于幼稚和静息记忆B细胞是低增殖的,但保留了相似的抗体分泌能力。结论:CD 2(-)CD 21(-)组织样记忆性B细胞增殖耗尽后在丙肝和非丙肝患者中循环频率增加该B细胞亚群没有表现出无反应性,在CD 40激动作用下表现出免疫球蛋白分泌能力,与其他CD 27/CD 21定义的B细胞亚群无法区分。爱思唯尔公司出版
Hepatitis C cirrhosis is associated with a profound disappearance of memory B-cells. We sought to determine if this loss is associated with the expansion of the CD27(-)CD21(-) tissue-like memory B-cells with features of B-cell exhaustion. To this end, we quantified the frequency of CD27(-) CD21(-) B-cells in healthy, non-cirrhotic HCV-infected, and cirrhotic patients. We examined the expression of putative inhibitory receptors, the proliferative and immunoglobulin-secreting capacity of CD27/CD21-defined B-cell subsets upon B-cell receptor and/or CD40 stimulation. We found that CD27(-)CD21(-) B-cells are significantly increased in frequency relative to healthy donors in HCV-infected patients. CD2(-)CD21(-) B-cells were hypoproliferative relative to nave and resting Memory B-cells upon agonistic stimulation, but retained similar capacity for antibody secretion. Conclusion: CD2(-)CD21(-) tissue-like memory B-cells with exhausted proliferation circulate at increased frequency in cirrhotic and non-cirrhotic HCV-infected patients. This B-cell subset does not appear anergic, exhibiting immunoglobulin-secreting capacity on CD40 agonism indistinguishable from other CD27/CD21-defined B-cell subsets. Published by Elsevier Inc.