Key Points Human IgG subclasses elicit distinct cytokine profiles by myeloid immune cells. Subclass-specific effects are mediated by distinct metabolic reprogramming by FcγRs. IgG subclasses provide pathogen- and cell type–specific immunity. IgG Abs are crucial for various immune functions, including neutralization, phagocytosis, and Ab-dependent cellular cytotoxicity. In this study, we identified another function of IgG by showing that IgG immune complexes elicit distinct cytokine profiles by human myeloid immune cells, which are dependent on FcγR activation by the different IgG subclasses. Using monoclonal IgG subclasses with identical Ag specificity, our data demonstrate that the production of Th17-inducing cytokines, such as TNF, IL-1β, and IL-23, is particularly dependent on IgG2, whereas type I IFN responses are controlled by IgG3, and IgG1 is able to regulate both. In addition, we identified that subclass-specific cytokine production is orchestrated at the posttranscriptional level through distinct glycolytic reprogramming of human myeloid immune cells. Combined, these data identify that IgG subclasses provide pathogen- and cell type–specific immunity through differential metabolic reprogramming by FcγRs. These findings may be relevant for future design of Ab-related therapies in the context of infectious diseases, chronic inflammation, and cancer.

中文翻译：

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IgG 亚类通过差异代谢重编程塑造人骨髓免疫细胞的细胞因子反应

关键点 人 IgG 亚类通过骨髓免疫细胞引发不同的细胞因子谱。亚类特异性效应由 FcγR 的不同代谢重编程介导。IgG 亚类提供病原体和细胞类型特异性免疫。IgG Ab 对各种免疫功能至关重要，包括中和、吞噬作用和依赖于 Ab 的细胞毒性。在本研究中，我们通过显示 IgG 免疫复合物通过人骨髓免疫细胞引发不同的细胞因子谱，确定了 IgG 的另一个功能，这些细胞因子谱依赖于不同 IgG 亚类对 FcγR 的激活。使用具有相同 Ag 特异性的单克隆 IgG 亚类，我们的数据表明 Th17 诱导细胞因子（如 TNF、IL-1β 和 IL-23）的产生特别依赖于 IgG2，而 I 型 IFN 反应受 IgG3 控制，和 IgG1 能够调节两者。此外，我们发现亚类特异性细胞因子的产生是通过人类骨髓免疫细胞的不同糖酵解重编程在转录后水平协调的。综合起来，这些数据表明 IgG 亚类通过 FcγR 的差异代谢重编程提供病原体和细胞类型特异性免疫。这些发现可能与传染病、慢性炎症和癌症背景下的 Ab 相关疗法的未来设计有关。这些数据表明 IgG 亚类通过 FcγR 的差异代谢重编程提供病原体和细胞类型特异性免疫。这些发现可能与传染病、慢性炎症和癌症背景下的 Ab 相关疗法的未来设计有关。这些数据表明 IgG 亚类通过 FcγR 的差异代谢重编程提供病原体和细胞类型特异性免疫。这些发现可能与传染病、慢性炎症和癌症背景下的 Ab 相关疗法的未来设计有关。