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Widespread B cell perturbations in HIV-1 infection afflict naive and marginal zone B cells.
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2019-06-20 , DOI: 10.1084/jem.20181124 Thomas Liechti 1 , Claus Kadelka 1, 2 , Dominique L Braun 1, 2 , Herbert Kuster 1, 2 , Jürg Böni 1 , Melissa Robbiani 3 , Huldrych F Günthard 1, 2 , Alexandra Trkola 4
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2019-06-20 , DOI: 10.1084/jem.20181124 Thomas Liechti 1 , Claus Kadelka 1, 2 , Dominique L Braun 1, 2 , Herbert Kuster 1, 2 , Jürg Böni 1 , Melissa Robbiani 3 , Huldrych F Günthard 1, 2 , Alexandra Trkola 4
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Perturbations in B cells are a hallmark of HIV-1 infection. This is signified by increased numbers of exhausted CD21neg memory B cells, driven by continuous antigen-specific and bystander activation. Using high-dimensional flow cytometry, we demonstrate that this exhausted phenotype is also prevalent among peripheral antigen-inexperienced naive and marginal zone (MZ) B cells in acute and chronic HIV-1 infection. A substantial fraction of naive and MZ B cells exhibit down-regulated CD21 levels and diminished response to B cell receptor (BCR)-dependent stimulation. Compared with CD21pos subsets, the CD21neg naive and MZ B cells differ in the expression of chemokine receptors and activation markers. Effective antiretroviral treatment normalizes peripheral naive and MZ B cell populations. Our results emphasize a more widely spread impairment of B cells in HIV-1 infection than previously appreciated, including antigen-inexperienced cells. This highlights the importance of monitoring functional capacities of naive B cells in HIV-1 infection, as exhausted CD21neg naive B cells may severely impair induction of novel B cell responses.
中文翻译：
HIV-1感染中广泛的B细胞扰动困扰着幼稚和边缘区B细胞。
B细胞的摄动是HIV-1感染的标志。这是由持续的抗原特异性和旁观者激活驱动的耗尽的CD21neg记忆B细胞数量增加所表示的。使用高维流式细胞仪，我们证明这种精疲力竭的表型在急性和慢性HIV-1感染的外周抗原缺乏经验的幼稚和边缘区（MZ）B细胞中也很普遍。幼稚和MZ B细胞的很大一部分显示出下调的CD21水平，并减弱了对B细胞受体（BCR）依赖性刺激的反应。与CD21pos亚群相比，CD21neg幼稚和MZ B细胞在趋化因子受体和激活标志物的表达上有所不同。有效的抗逆转录病毒治疗可使外周血幼稚和MZ B细胞群体正常化。我们的结果强调，HIV-1感染中B细胞的损伤分布比以前所认识的更广泛，包括抗原缺乏的细胞。这凸显了监视HIV-1感染中的原始B细胞功能能力的重要性，因为用尽的CD21neg原始B细胞可能会严重损害新型B细胞应答的诱导。
更新日期：2019-09-03
中文翻译：
HIV-1感染中广泛的B细胞扰动困扰着幼稚和边缘区B细胞。
B细胞的摄动是HIV-1感染的标志。这是由持续的抗原特异性和旁观者激活驱动的耗尽的CD21neg记忆B细胞数量增加所表示的。使用高维流式细胞仪，我们证明这种精疲力竭的表型在急性和慢性HIV-1感染的外周抗原缺乏经验的幼稚和边缘区（MZ）B细胞中也很普遍。幼稚和MZ B细胞的很大一部分显示出下调的CD21水平，并减弱了对B细胞受体（BCR）依赖性刺激的反应。与CD21pos亚群相比，CD21neg幼稚和MZ B细胞在趋化因子受体和激活标志物的表达上有所不同。有效的抗逆转录病毒治疗可使外周血幼稚和MZ B细胞群体正常化。我们的结果强调，HIV-1感染中B细胞的损伤分布比以前所认识的更广泛，包括抗原缺乏的细胞。这凸显了监视HIV-1感染中的原始B细胞功能能力的重要性，因为用尽的CD21neg原始B细胞可能会严重损害新型B细胞应答的诱导。
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