Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
Glycoscience Research Laboratory, Genos Ltd., Zagreb, Croatia.
Sci Rep. 2021 Dec 15;11(1):24045. doi: 10.1038/s41598-021-03196-w.
As a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography-mass spectrometry (LC-MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells.
作为一个淋巴器官，脾脏容纳了广泛的免疫细胞群体，这些细胞不仅清除血液中的抗原，还产生和调节抗原特异性免疫反应。特别是，脾脏微环境已被证明在包膜病毒感染和同种抗原的适应性免疫反应中发挥重要作用。在这两种免疫接种中，抗原特异性免疫球蛋白 G（IgG）的特征是 Fc 区域 N 连接聚糖上存在的岩藻糖减少。这些糖基对于介导免疫效应功能的诱导至关重要。因此，我们假设脾脏可能调节体液反应，并作为去岩藻糖 IgG 反应的优先部位，这可能在免疫性血小板减少症（ITP）发病机制中发挥作用。为了确定脾脏在 IgG-Fc 糖基化中的作用，我们对因创伤、ITP 或遗传性球形红细胞增多症而接受脾切除术的大量个体进行了 IgG 亚类特异性液相色谱-质谱（LC-MS）分析，以确定 Fc 糖基化的 IgG 亚类特异性。脾切除术后 IgG-Fc 岩藻糖基化始终增加，而 IgG-Fc 半乳糖基化和唾液酸化则没有影响。我们首次报道了脾切除术后 IgG1 和 IgG2/3-Fc 岩藻糖基化水平增加，这表明脾脏中发生的免疫反应可能特别容易产生去岩藻糖 IgG 反应。令人惊讶的是，与健康对照组相比，ITP 患者的总 IgG-Fc 岩藻糖基化水平降低。总体而言，我们的研究结果表明，脾脏在 B 细胞产生去岩藻糖 IgG 反应的诱导或维持中具有尚未被认识的作用。
