小柯机器人

靶向B细胞中的BMI-1可恢复有效的体液免疫反应并控制慢性病毒感染
2021-11-30 15:50

澳大利亚莫纳什大学Kim L. Good-Jacobson研究组发现,靶向B细胞中的BMI-1可恢复有效的体液免疫反应并控制慢性病毒感染。这一研究成果于2021年11月29日在线发表在国际学术期刊《自然—免疫学》上。

研究人员发现,在小鼠中靶向表观遗传修饰蛋白BMI-1能改善对慢性淋巴细胞性脉络膜炎病毒的体液反应。与急性感染相比,BMI-1在慢性病毒感染中被生发中心B细胞上调,与可及性染色质景观的变化相关。B细胞本身的Bmi1缺失加速了病毒的清除,减少了脾脏肿大,并恢复了脾脏结构。Bmi1的缺失恢复了B细胞中c-Myc的表达,伴随着抗体质量的提高,同时分泌抗体的细胞数量减少。

具体来说,BMI-1缺陷诱导的抗体具有更强的中和能力和增强的抗体依赖性效应功能。通过使用一种小分子抑制剂来抑制小鼠的BMI-1,研究人员可以消耗抗体分泌细胞,并禁止体内有害免疫复合物的形成。这项研究将BMI-1定义为控制慢性感染中抗体介导反应的关键免疫调节因子。

据悉,无效抗体介导的反应是慢性病毒感染的一个关键特征。然而,人们对驱动这种失调机制的理解还不清楚。

附:英文原文

Title: Targeting BMI-1 in B cells restores effective humoral immune responses and controls chronic viral infection

Author: Di Pietro, Andrea, Polmear, Jack, Cooper, Lucy, Damelang, Timon, Hussain, Tabinda, Hailes, Lauren, ODonnell, Kristy, Udupa, Vibha, Mi, Tian, Preston, Simon, Shtewe, Areen, Hershberg, Uri, Turner, Stephen J., La Gruta, Nicole L., Chung, Amy W., Tarlinton, David M., Scharer, Christopher D., Good-Jacobson, Kim L.

Issue&Volume: 2021-11-29

Abstract: Ineffective antibody-mediated responses are a key characteristic of chronic viral infection. However, our understanding of the intrinsic mechanisms that drive this dysregulation are unclear. Here, we identify that targeting the epigenetic modifier BMI-1 in mice improves humoral responses to chronic lymphocytic choriomeningitis virus. BMI-1 was upregulated by germinal center B cells in chronic viral infection, correlating with changes to the accessible chromatin landscape, compared to acute infection. B cell-intrinsic deletion of Bmi1 accelerated viral clearance, reduced splenomegaly and restored splenic architecture. Deletion of Bmi1 restored c-Myc expression in B cells, concomitant with improved quality of antibody and coupled with reduced antibody-secreting cell numbers. Specifically, BMI-1-deficiency induced antibody with increased neutralizing capacity and enhanced antibody-dependent effector function. Using a small molecule inhibitor to murine BMI-1, we could deplete antibody-secreting cells and prohibit detrimental immune complex formation in vivo. This study defines BMI-1 as a crucial immune modifier that controls antibody-mediated responses in chronic infection. Chronic viral infection leads to a dysregulation of germinal center B cell responses. Di Pietro et al. show that the epigenetic modifier BMI-1 promotes this dysfunctional response and that targeting BMI-1 in B cells can restore humoral immunity and accelerate viral clearance.

DOI: 10.1038/s41590-021-01077-y

Source: https://www.nature.com/articles/s41590-021-01077-y

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex


本期文章:《自然—免疫学》:Online/在线发表

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