Human follicular lymphoma cells contain oligomannose glycans in the antigen-binding site of the B-cell receptor
Human follicular lymphoma cells contain oligomannose glycans in the antigen-binding site of the B-cell receptor
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DOI：
10.1074/jbc.m602690200
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发表时间：
2007-03-09
影响因子：
4.8
通讯作者：
Stevenson, Freda K.
中科院分区：
文献类型：
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作者：
Radcliffe, Catherine M.;Arnold, James N.;Stevenson, Freda K.
表面免疫球蛋白的表达对于 B 细胞淋巴瘤的生长和存活至关重要。在滤泡性淋巴瘤中，我们之前发现 B 细胞受体中的 Ig 可变 (V) 区表达 N-糖基化序列片段 NX(S/T) 的发生率惊人地高。这些潜在的糖基化位点是通过体细胞突变引入的，并且是淋巴瘤特异性的，表明它们参与肿瘤发病机制。对淋巴瘤来源的 IgG/IgM 的 V 区糖进行分析表明，它们主要是寡甘露糖，并且值得注意的是，它们位于抗原结合位点，可能排除常规抗原结合。 Fc 区包含复杂的聚糖，证实正常的聚糖加工途径是完整的。结合研究表明，占据 V 区的寡甘露糖聚糖可与甘露糖结合凝集素接触。这些发现表明，淋巴瘤发病机制的潜在贡献涉及 B 细胞受体表面免疫球蛋白与生发中心先天免疫的甘露糖结合分子的抗原独立相互作用。
Expression of surface immunoglobulin appears critical for the growth and survival of B-cell lymphomas. In follicular lymphoma, we found previously that the Ig variable (V) regions in the B-cell receptor express a strikingly high incidence of N-glycosylation sequons, NX(S/T). These potential glycosylation sites are introduced by somatic mutation and are lymphoma-specific, pointing to their involvement in tumor pathogenesis. Analysis of the V region sugars from lymphoma-derived IgG/IgM reveals that they are mostly oligomannose and, remarkably, are located in the antigen-binding site, possibly precluding conventional antigen binding. The Fc region contains complex glycans, confirming that the normal glycan processing pathway is intact. Binding studies indicate that the oligomannose glycans occupying the V regions are accessible to mannose-binding lectin. These findings suggest a potential contribution to lymphoma pathogenesis involving antigen-independent interaction of surface immunoglobulin of the B-cell receptor with mannose-binding molecules of innate immunity in the germinal center.