Memory B cell dysregulation in HIV-1-infected individuals
Memory B cell dysregulation in HIV-1-infected individuals
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DOI：
10.1097/qad.0000000000001686
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发表时间：
2018-01-14
期刊：
影响因子：
3.8
通讯作者：
Blanco, Julia
中科院分区：
文献类型：
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作者：
Carrillo, Jorge;Negredo, Eugenia;Blanco, Julia
目的：探讨HIV-1感染和抗逆转录病毒治疗（ART）对人类记忆B（MEB）细胞区室的影响。设计：采用横断面研究分析HIV-1（+）ART治疗和ART初治受试者以及未感染个体的MEB细胞。通过细胞培养和流式细胞术在体外评估自发细胞死亡和B细胞增殖能力。结果：HIV-1（+）ART治疗的受试者尽管缺乏IgM（+）IgD（+）CD 27（+）边缘带样B细胞的恢复，但没有表现出功能性脾功能减退。此外，HIV-1（+）个体中的两个生发中心依赖性MEB细胞亚群也出现失调：IgM（+）IgD（-）CD 27（+）（仅限IgM）细胞增加，而病毒血症个体中转换的亚群（IgM（-）IgD（-））减少。尽管ART恢复了这些群体的数量，但转换的MEB细胞富含CD 27（-）细胞，其显示出离体自发细胞死亡的最高易感性。此外，病毒血症个体的B细胞表现出对B细胞受体和Toll样受体9刺激的不良反应，当同时使用这两种刺激时，这种反应被规避。结论：HIV-1（+）研究参与者的B细胞表现出不良的刺激能力，这可能被适当的刺激组合所绕过，以及一个失调的ME B细胞库，这表明生殖中心反应的影响，仅部分由ART恢复正常。有趣的是，脾功能减退不能解释ART治疗的HIV-1（+）个体中边缘区样B细胞的恢复缺乏。
Objective:To characterize the effect of the HIV-1 infection and antiretroviral treatment (ART) in the human memory B (MEB)-cell compartment.Design:A cross-sectional study was designed to analyze MEB cells of HIV-1(+) ART treated and ART-naive study participants, and uninfected individuals.Methods:Frequency and absolute counts of MEB cell subsets in blood were determined by multicolor flow cytometry. Spontaneous cell death and B-cell proliferative capacity was evaluated in vitro by cell culture and flow cytometry. Splenic function was determined by pitted erythrocytes quantification in HIV-1(+) ART-treated study participants.Results:HIV-1(+) ART-treated individuals did not show functional hyposplenism despite the lack of recovery IgM(+)IgD(+)CD27(+) marginal zone-like B cells. Moreover, two germinal center-dependent MEB cells subsets were also dysregulated in HIV-1(+) individuals: IgM(+)IgD(-)CD27(+) (IgM only) cells were increased, whereas the switched subset (IgM(-)IgD(-)) was reduced in viremic individuals. Althought ART restored the numbers of these populations; the switched MEB cells were enriched in CD27(-) cells, which showed the highest susceptibility to spontaneous cell death ex vivo. In addition, B cells from viremic individuals showed a poor response to B-cell receptor and toll-like receptor 9 stimulation that was circumvented when both stimuli were used simultaneously.Conclusion:B cells from HIV-1(+) study participants show a poor stimulation capacity, that may be bypassed by the proper combination of stimuli, and a dysregulated MEB cell pool that suggest an affectation of the germinal center reaction, only partially normalized by ART. Interestingly, hyposplenism does not explain the lack of recovery of the marginal zone-like B cells in ART-treated HIV-1(+) individuals.