HIV infection induces inflammaging and chronic immune activation (IA), which are negatively associated with protective humoral immunity. Similar to HIV, aging is also associated with increased inflammaging and IA. The metabolic requirements of B cell responses in HIV infected (HIV+) individuals are not known, although metabolic abnormalities have been reported in these individuals. How these metabolic abnormalities are exacerbated by aging is also not known. B cells were isolated by magnetic sorting from the blood of young and elderly HIV + individuals, as well as from the blood of age-matched healthy controls. We evaluated the composition of the B cell pool by flow cytometry, the expression of RNA for pro-inflammatory and metabolic markers by qPCR and their metabolic status using a Seahorse XFp extracellular flux analyzer. In this study we have evaluated for the first time the metabolic phenotype of B cells from young and elderly HIV + individuals as compared to those obtained from age-matched healthy controls. Results show that the B cell pool of HIV + individuals is enriched in pro-inflammatory B cell subsets, expresses higher levels of RNA for pro-inflammatory markers and is hyper-metabolic, as compared to healthy controls, and more in elderly versus young HIV + individuals, suggesting that this higher metabolic phenotype of B cells is needed to support B cell IA. We have identified the subset of Double Negative (DN) B cells as the subset mainly responsible for this hyper-inflammatory and hyper-metabolic profile. Our results identify a relationship between intrinsic B cell inflammation and metabolism in HIV + individuals and suggest that metabolic pathways in B cells from HIV + individuals may be targeted to reduce inflammaging and IA and improve B cell function and antibody responses.

中文翻译：

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来自年轻和老年 HIV 个体的 B 细胞的代谢表型

HIV 感染诱导炎症和慢性免疫激活 (IA)，这与保护性体液免疫呈负相关。与 HIV 类似，衰老也与炎症和 IA 增加有关。HIV 感染 (HIV+) 个体中 B 细胞反应的代谢需求尚不清楚，尽管已经报道了这些个体的代谢异常。这些代谢异常如何因衰老而加剧也不得而知。B 细胞是通过磁性分选从年轻和老年 HIV + 个体的血液以及年龄匹配的健康对照的血液中分离出来的。我们通过流式细胞术评估了 B 细胞库的组成，通过 qPCR 评估了促炎和代谢标志物的 RNA 表达，并使用 Seahorse XFp 细胞外通量分析仪评估了它们的代谢状态。在这项研究中，我们首次评估了来自年轻和老年 HIV + 个体的 B 细胞的代谢表型与从年龄匹配的健康对照中获得的 B 细胞的代谢表型相比。结果表明，与健康对照相比，HIV + 个体的 B 细胞库富含促炎 B 细胞亚群，表达更高水平的促炎标志物 RNA，并且代谢亢进，并且在老年人与年轻 HIV 中更多+ 个体，表明需要这种更高的 B 细胞代谢表型来支持 B 细胞 IA。我们已将双阴性 (DN) B 细胞亚群确定为主要负责这种高炎症和高代谢特征的亚群。