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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins
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Glycosylation of surface Ig creates a functional bridge between human follicular lymphoma and microenvironmental lectins

机译：表面Ig的糖基化在人滤泡性淋巴瘤和微环境凝集素之间建立功能性桥梁

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摘要

Surface Ig (slg) of follicular lymphoma (FL) is vital for tumor cell survival. We found previously that the Ig in FL is unusual, because the variable region genes carry sequence motifs for N-glycan addition. These are introduced by somatic mutation and are tumor specific. Unexpectedly, added glycans terminate at high mannose, suggesting a potentially important interaction of FL cells with mannose-binding lectins of the innate immune system. We have now identified mannosylated IgM at the surface of primary lymphoma cells. Recombinant lectin domains of the mannose receptor (MR) or DC-SIGN bind mannosylated Igs in vitro and bind to FL cells, signaling slgM-associated increases in intracellular Ca~（2+）. Lectins also bind to normal B cells but fail to signal. In contrast, anti-lg signaled similarly in both FL and normal B cells. Mannosylation patterns were mimicked by FL Ig-derived single-chain Fvs (scFv), providing probes for potential receptors. Mannosylated scFv bound specifically to the lectin domains of the MR and DC-SIGN and blocked signaling. Mannosylated scFv also bound to DC-SIGN on the surface of dendritic cells. This unique lymphoma-specific interaction of slg with lectins of innate immunity reveals a potential route for microenvironmental support of tumor cells, mediated via the key B-cell receptor.
机译：滤泡性淋巴瘤（FL）的表面Ig（slg）对肿瘤细胞存活至关重要。我们先前发现FL中的Ig是不寻常的，因为可变区基因带有N-聚糖添加的序列基序。这些是通过体细胞突变引入的，并且是肿瘤特异性的。出乎意料的是，添加的聚糖在高甘露糖处终止，表明FL细胞与先天免疫系统的甘露糖结合凝集素之间潜在的重要相互作用。现在，我们已经在原发性淋巴瘤细胞表面鉴定出了甘露糖基化的IgM。甘露糖受体（MR）或DC-SIGN的重组凝集素结构域在体外与甘露糖基化的Igs结合并与FL细胞结合，表明slgM相关的细胞内Ca〜（2+）增加。凝集素也结合正常的B细胞，但不能发信号。相反，抗Ig1在FL和正常B细胞​​中的信号相似。甘露糖基化模式被FL Ig衍生的单链Fv（scFv）模仿，提供了潜在受体的探针。甘露糖基化的scFv特异地结合到MR和DC-SIGN的凝集素结构域，并阻断信号传导。甘露糖基化的scFv也与树突状细胞表面的DC-SIGN结合。 slg与先天免疫凝集素的这种独特的淋巴瘤特异性相互作用揭示了通过关键B细胞受体介导的肿瘤细胞微环境支持的潜在途径。

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    Vania Coelho; Sergey Krysov; Amir M. Ghaemmaghami; Mohamed Emara; Kathleen N. Potter; Peter Johnson; Graham Packham; Luisa Martinez-Pomares; Freda K. Stevenson;

  • 作者单位

    Molecular Immunology Group, Cancer Sciences Division, University of Southampton, School of Medicine, Southampton SO16 6YD, United Kingdom;

    rnMolecular Immunology Group, Cancer Sciences Division, University of Southampton, School of Medicine, Southampton SO16 6YD, United Kingdom;

    rnSchool of Molecular Medical Sciences, Institute of Infection, Immunity and Inflammation, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, United Kingdom;

    rnSchool of Molecular Medical Sciences, Institute of Infection, Immunity and Inflammation, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, United Kingdom;

    rnMolecular Immunology Group, Cancer Sciences Division, University of Southampton, School of Medicine, Southampton SO16 6YD, United Kingdom;

    rnMolecular Immunology Group, Cancer Sciences Division, University of Southampton, School of Medicine, Southampton SO16 6YD, United Kingdom;

    rnMolecular Immunology Group, Cancer Sciences Division, University of Southampton, School of Medicine, Southampton SO16 6YD, United Kingdom;

    rnSchool of Molecular Medical Sciences, Institute of Infection, Immunity and Inflammation, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, United Kingdom;

    rnMolecular Immunology Group, Cancer Sciences Division, University of Southampton, School of Medicine, Southampton SO16 6YD, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    B cell; B-cell receptor; B-cell lymphoma; immunoglobulin;

    机译：B细胞;B细胞受体;B细胞淋巴瘤;免疫球蛋白;

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