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首页> 外文期刊>Molecular and Cellular Biology >ST6Gal-I Restrains CD22-Dependent Antigen Receptor Endocytosis and Shp-1 Recruitment in Normal and Pathogenic Immune Signaling
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ST6Gal-I Restrains CD22-Dependent Antigen Receptor Endocytosis and Shp-1 Recruitment in Normal and Pathogenic Immune Signaling

机译：ST6Gal-I抑制正常和病原性免疫信号传导中CD22依赖性抗原受体的内吞作用和Shp-1募集。

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摘要

The ST6Gal-I sialyltransferase produces Siglec ligands for the B-cell-specific CD22 lectin and sustains humoral immune responses. Using multiple experimental approaches to elucidate the mechanisms involved, we report that ST6Gal-I deficiency induces immunoglobulin M (IgM) antigen receptor endocytosis in the absence of immune stimulation. This coincides with increased antigen receptor colocalization with CD22 in both clathrin-deficient and clathrin-enriched membrane microdomains concurrent with diminished tyrosine phosphorylation of Igα/β, Syk, and phospholipase C-γ2 upon immune activation. Codeficiency with CD22 restores IgM antigen receptor half-life at the cell surface in addition to reversing alterations in membrane trafficking and immune signaling. Diminished immune responses due to ST6Gal-I deficiency further correlate with constitutive recruitment of Shp-1 to CD22 in unstimulated B cells independent of Lyn tyrosine kinase activity and prevent autoimmune disease pathogenesis in the Lyn-deficient model of systemic lupus erythematosus, resulting in a significant extension of life span. Protein glycosylation by ST6Gal-I restricts access of antigen receptors and Shp-1 to CD22 and operates by a CD22-dependent mechanism that decreases the basal rate of IgM antigen receptor endocytosis in altering the threshold of B-cell immune activation.
机译：ST6Gal-1唾液酸转移酶为B细胞特异性CD22凝集素产生Siglec配体，并维持体液免疫反应。使用多种实验方法来阐明所涉及的机制，我们报告说ST6Gal-1缺乏会在没有免疫刺激的情况下诱导免疫球蛋白M（IgM）抗原受体的内吞作用。这与在缺乏网格蛋白的膜和富含网格蛋白的膜微域中与CD22的抗原受体共定位增加同时免疫免疫激活后Igα/β，Syk和磷脂酶C-γ2的酪氨酸磷酸化减少有关。除逆转膜运输和免疫信号的改变外，CD22的编码缺陷还恢复了细胞表面IgM抗原受体的半衰期。 ST6Gal-I缺乏引起的免疫应答降低还与非刺激性B细胞中独立于Lyn酪氨酸激酶活性的Shp-1组成性募集CD22相关联，并在系统性红斑狼疮Lyn缺陷模型中预防自身免疫性疾病的发病机制，从而导致显着延长寿命。 ST6Gal-1的蛋白质糖基化作用限制了抗原受体和Shp-1进入CD22，并通过CD22依赖性机制起作用，该机制在改变B细胞免疫激活阈值时降低了IgM抗原受体内吞的基础速率。

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