Department of Cell Biology, IFOM ETS-The AIRC Institute of Molecular Oncology, Via Adamello, 16, 20139 Milan, Italy.
The Department for Welding Production and Technology of Constructional Materials, Perm National Research Polytechnic University, Komsomolsky Prospekt, 29, 614990 Perm, Russia.
Int J Mol Sci. 2023 Oct 10;24(20):15044. doi: 10.3390/ijms242015044.
The system of the four different human blood groups is based on the oligosaccharide antigens A or B, which are located on the surface of blood cells and other cells including endothelial cells, attached to the membrane proteins or lipids. After transfusion, the presence of these antigens on the apical surface of endothelial cells could induce an immunological reaction against the host. The final oligosaccharide sequence of AgA consists of Gal-GlcNAc-Gal (GalNAc)-Fuc. AgB contains Gal-GlcNAc-Gal (Gal)-Fuc. These antigens are synthesised in the Golgi complex (GC) using unique Golgi glycosylation enzymes (GGEs). People with AgA also synthesise antibodies against AgB (group A [II]). People with AgB synthesise antibodies against AgA (group B [III]). People expressing AgA together with AgB (group AB [IV]) do not have these antibodies, while people who do not express these antigens (group O [0; I]) synthesise antibodies against both antigens. Consequently, the antibodies are synthesised against antigens that apparently do not exist in the body. Here, we compared the prediction power of the main hypotheses explaining the formation of these antibodies, namely, the concept of natural antibodies, the gut bacteria-derived antibody hypothesis, and the antibodies formed as a result of glycosylation mistakes or de-sialylation of polysaccharide chains. We assume that when the GC is overloaded with lipids, other less specialised GGEs could make mistakes and synthesise the antigens of these blood groups. Alternatively, under these conditions, the chylomicrons formed in the enterocytes may, under this overload, linger in the post-Golgi compartment, which is temporarily connected to the endosomes. These compartments contain neuraminidases that can cleave off sialic acid, unmasking these blood antigens located below the acid and inducing the production of antibodies.
四种不同人类血型系统基于寡糖抗原 A 或 B，这些抗原位于细胞表面和其他细胞上，包括内皮细胞，附着在膜蛋白或脂质上。输血后，内皮细胞顶表面存在这些抗原可诱导针对宿主的免疫反应。AgA 的最终寡糖序列由 Gal-GlcNAc-Gal（GalNAc）-Fuc 组成。AgB 含有 Gal-GlcNAc-Gal（Gal）-Fuc。这些抗原在高尔基复合体 (GC) 中使用独特的高尔基糖基化酶 (GGE) 合成。具有 AgA 的人也会合成针对 AgB 的抗体（A 组 [II]）。具有 AgB 的人会合成针对 AgA 的抗体（B 组 [III]）。同时表达 AgA 和 AgB 的人（AB 组 [IV]）没有这些抗体，而不表达这些抗原的人（O 组 [0；I]）会合成针对这两种抗原的抗体。因此，这些抗体是针对显然不存在于体内的抗原合成的。在这里，我们比较了解释这些抗体形成的主要假设的预测能力，即天然抗体概念、肠道细菌衍生的抗体假说以及由于糖基化错误或多糖链去唾液酸化形成的抗体。我们假设，当 GC 被脂质过度负载时，其他不太专门的 GGE 可能会出错并合成这些血型的抗原。或者，在这些条件下，在这些超负荷下形成的乳糜微粒可能会在高尔基后区室中徘徊，该后区室暂时与内体连接。这些隔室包含可以切断唾液酸的神经氨酸酶，从而暴露出位于酸下方的这些血型抗原，并诱导抗体的产生。
