Human B-lymphocytes express α2-6-sialylated 6-sulfo-N-acetyllactosamine serving as a preferred ligand for CD22/Siglec-2
Human B-lymphocytes express α2-6-sialylated 6-sulfo-N-acetyllactosamine serving as a preferred ligand for CD22/Siglec-2
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DOI：
10.1074/jbc.m702341200
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发表时间：
2007-11-02
影响因子：
4.8
通讯作者：
Kannagi, Reiji
中科院分区：
文献类型：
--
作者：
Kimura, Naoko;Ohmori, Katsuyuki;Kannagi, Reiji
CD22/Siglec-2是B淋巴细胞上一种重要的抑制共受体，它识别α2-6-唾液酸糖作为一种特异性配体。在这里，我们认为α2-6-唾液酸化和6-GlcNAc-磺化决定簇是CD22的首选配基，因为人B细胞系与CD22的结合在与细胞硫酸盐代谢抑制剂NaClO_3孵育后几乎完全被取消，并且也被新产生的针对α2-6-唾液酸化的6-磺基-N-乙酰乳糖胺(LacNAc)决定簇(KN343，小鼠IgM)的单抗显著抑制。该抗体所定义的α2-6-唾液酸化6-磺基-LacNAc决定簇在大多数正常人外周B淋巴细胞和周围淋巴结滤泡性B淋巴细胞上均有显著表达。在次级淋巴组织(包括淋巴结、扁桃体和肠相关淋巴组织)的高内皮微静脉内皮细胞中，CD22的表达强于B淋巴细胞，提示CD22在B细胞与血管的相互作用和转运中起作用。这些结果表明，α2-6-唾液酸化的6-磺酸-LacNAc决定簇是人CD22的内源性配体，提示6-GlcNAc硫化和α2-6-唾液酸化可能调节人CD22/Siglec-2的功能。
CD22/Siglec-2, an important inhibitory co-receptor on B-lymphocytes, is known to recognize alpha 2-6-sialylated glycan as a specific ligand. Here we propose that the alpha 2-6-sialylated and 6-GlcNAc-sulfated determinant serves as a preferred ligand for CD22 because the binding of a human B-cell line to CD22 was almost completely abrogated after incubating the cells with NaClO3, an inhibitor of cellular sulfate metabolism, and was also significantly inhibited by a newly generated monoclonal antibody specific to the alpha 2-6-sialylated 6-sulfo-N-acetyllactosamine ( LacNAc) determinant ( KN343, murine IgM). The alpha 2-6-sialylated 6-sulfo-LacNAc determinant defined by the antibody was significantly expressed on a majority of normal human peripheral B-lymphocytes as well as follicular B-lymphocytes in peripheral lymph nodes. The determinant was also expressed in endothelial cells of high endothelial venules of secondary lymphoid tissues, including lymph nodes, tonsils, and intestine-associated lymphoid tissues, more strongly than on B-lymphocytes, suggesting a role for CD22 in B-cell interaction with blood vessels and trafficking. These results indicate that the alpha 2-6-sialylated 6-sulfo-LacNAc determinant serves as an endogenous ligand for human CD22 and suggest the possibility that 6-GlcNAc sulfation as well as alpha 2-6-sialylation may regulate CD22/Siglec-2 functions in humans.