Effect of Antiretroviral Therapy on the Memory and Activation Profiles of B Cells in HIV-Infected African Women.
Effect of Antiretroviral Therapy on the Memory and Activation Profiles of B Cells in HIV-Infected African Women.
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抗逆转录病毒疗法对HIV感染的非洲妇女B细胞的记忆和激活谱的影响。
DOI：
10.4049/jimmunol.1601560
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发表时间：
2017-02-01
期刊：
影响因子：
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通讯作者：
Burgers WA
中科院分区：
文献类型：
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作者：
Tanko RF;Soares AP;Müller TL;Garrett NJ;Samsunder N;Abdool Karim Q;Abdool Karim SS;Riou C;Burgers WA
HIV 感染会对 B 细胞产生广泛的影响，包括记忆细胞分化失常、B 细胞功能受损和高丙种球蛋白血症。然而，抗逆转录病毒疗法 (ART) 在多大程度上可以逆转这些 B 细胞异常的数据有限。为了研究 ART 对 B 细胞的影响，使用流式细胞术纵向测量了 19 名 HIV 感染者在 ART 开始前（中位，2 个月）和后（中位，12 个月）的 B 细胞活化（CD86）和分化（IgD、CD27 和 CD38）谱，并与 19 名年龄匹配的未感染 HIV 的个体进行比较。 12个月的ART恢复了B细胞亚群的典型分布，增加了幼稚B细胞（CD27−IgD+CD38−）的比例，同时减少了未成熟过渡细胞（CD27−IgD+CD38+）、未转换记忆（CD27+IgD+CD38−）、转换记忆（CD27+IgD−CD38−或CD27−IgD−CD38−）和浆母细胞 (CD27+IgD−CD38high) 亚群。然而，ART 后 B 细胞活化仅部分正常化，活化 B 细胞 (CD86+CD40+) 的频率与 ART 前水平相比有所降低 (p=0.0001)，但与未感染 HIV 的个体相比仍显着较高 (p=0.0001)。有趣的是，与 T 细胞激活谱不同，ART 之前的 B 细胞激活程度与 HIV 血浆病毒载量无关，但与血浆 sCD14 水平呈正相关（p=0.01，r=0.58）。总体而言，ART 部分使 HIV 诱导的 B 细胞分布正常化，并且某些激活持续存在。了解 HIV 对 ART 后 B 细胞功能障碍和恢复的影响可能为了解 HIV 发病机制提供重要见解。
HIV infection induces a wide range of effects in B cells, including skewed memory cell differentiation, compromised B cell function and hypergammaglobulinaemia. However, data on the extent to which these B cell abnormalities can be reversed by antiretroviral therapy (ART) are limited. To investigate the effect of ART on B cells, the activation (CD86) and differentiation (IgD, CD27 and CD38) profiles of B cells were measured longitudinally in 19 HIV-infected individuals before (median, 2 months) and after ART initiation (median, 12 months) and compared to 19 age-matched HIV-uninfected individuals, using flow cytometry. Twelve months of ART restored the typical distribution of B cell subsets, increasing the proportion of naive B cells (CD27−IgD+CD38−) and concomitantly decreasing the immature transitional (CD27−IgD+CD38+), unswitched memory (CD27+IgD+CD38−), switched memory (CD27+IgD−CD38− or CD27−IgD−CD38−) and plasmablast (CD27+IgD−CD38high) subsets. However, B cell activation was only partially normalized post-ART, with the frequency of activated B cells (CD86+CD40+) reduced compared to pre-ART levels (p=0.0001), but remaining significantly higher compared to HIV-uninfected individuals (p=0.0001). Interestingly, unlike for T cell activation profiles, the extent of B cell activation prior to ART did not correlate with HIV plasma viral load, but positively associated with plasma sCD14 levels (p=0.01, r=0.58). Overall, ART partially normalizes the skewed B cell profiles induced by HIV, with some activation persisting. Understanding the effect of HIV on B cell dysfunction and restoration following ART may provide important insights into mechanisms of HIV pathogenesis.