T cell-independent B cell activation induces immunosuppressive sialylated IgG antibodies
T cell-independent B cell activation induces immunosuppressive sialylated IgG antibodies
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DOI：
10.1172/jci65938
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发表时间：
2013-09-01
影响因子：
15.9
通讯作者：
Ehlers, Marc
中科院分区：
文献类型：
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作者：
Hess, Constanze;Winkler, Andre;Ehlers, Marc
抗原特异性抗体能够增强或抑制免疫应答，这取决于它们结合在免疫细胞上的受体。最近的研究表明，IgG Ab的前效应子或后效应子功能也通过其Fc N-连接的糖基化模式进行调节。无半乳糖基化的IgG抗体。（非半乳糖基化的）和去唾液酸化的是促炎性的，并且由T细胞依赖性（TD）蛋白抗原和促炎性共刺激的组合诱导。免疫抑制性唾液酸化IgG Ab和TcAb在耐受性条件下存在TD抗原时产生。通过多糖交联的B细胞受体（BCR）或通过BCR和TLR共刺激的T细胞非依赖性（TI）B细胞活化也诱导IgG Ab，但这些Ab的Fc糖基化状态未知。我们在小鼠实验中发现，TI免疫应答诱导抑制性唾液酸化。IgG，与TD促炎性Th 1和Th 17免疫应答相反，其诱导无半乳糖基化和去唾液酸化IgG。少量抗原特异性唾液酸化IgG Ab的转移足以抑制B细胞活化和致病性免疫反应。这些发现表明通过产生免疫抑制唾液酸化的TI免疫应答的免疫调节功能。IgG，并可能提供对感染，疫苗接种和自身免疫过程中TI免疫反应的作用的见解。
Antigen-specific Abs are able to enhance or suppress immune responses depending on the receptors that they bind on immune cells. Recent studies have shown that pro- or antiinflammatory effector functions of IgG Abs are also regulated through their Fc N-linked glycosylation patterns. IgG Abs that are agalactosylated. (non-galactosylated) and asialylated are proinflammatory and induced by the combination of T cell-dependent (TD) protein antigens and proinflammatory costimulation. Sialylated IgG Abs, which are immunosuppressive, and Tregs are produced in the presence of TD antigens under tolerance conditions. T cell-independent (TI) B cell activation via B cell receptor (BCR) crosslinking through polysaccharides or via BCR and TLR costimulation also induces IgG Abs, but the Fc glycosylation state of these Abs is unknown. We found in mouse experiments that TI immune responses induced suppressive sialylated. IgGs, in contrast to TD proinflammatory Th1 and Th17 immune responses, which induced agalactosylated and asialylated IgGs. Transfer of low amounts of antigen-specific sialylated IgG Abs was sufficient to inhibit B cell activation and pathogenic immune reactions. These findings suggest an immune regulatory function for TI immune responses through the generation of immunosuppressive sialylated. IgGs and may provide insight on the role of TI immune responses during infection, vaccination, and autoimmunity.