Ligation of tumour-produced mucins to CD22 dramatically impairs splenic marginal zone B-cells.
Ligation of tumour-produced mucins to CD22 dramatically impairs splenic marginal zone B-cells.
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DOI：
10.1042/bj20081241
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发表时间：
2009-02
期刊：
影响因子：
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通讯作者：
Munetoyo Toda;Risa Hisano;H. Yurugi;Kaoru Akita;K. Maruyama;M. Inoue;T. Adachi;T. Tsubata;H. Nakada
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文献类型：
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作者：
Munetoyo Toda;Risa Hisano;H. Yurugi;Kaoru Akita;K. Maruyama;M. Inoue;T. Adachi;T. Tsubata;H. Nakada
CD 22 [Siglec-2（唾液酸结合，免疫球蛋白样凝集素-2）]是B细胞信号传导的负调节因子，与α 2，6-唾液酸连接的糖缀合物结合，包括唾液酸-Tn抗原，其是在各种粘蛋白上表达的典型肿瘤相关碳水化合物抗原之一。许多上皮肿瘤将粘蛋白分泌到组织和/或血流中。小鼠乳腺腺癌细胞TA 3-Ha产生一种名为epiglycanin的粘蛋白，但它们的一个亚系TA 3-St不产生这种粘蛋白。表聚糖结合CD 22并在体外抑制B细胞信号传导。使用这些细胞系研究了粘蛋白在荷瘤状态下的体内作用。应该注意的是，在携带TA 3-Ha细胞的小鼠中，脾脏MZ（边缘区）B细胞显著减少，但在携带TA 3-St细胞的小鼠中没有，这与这些小鼠中胸腺非依赖性应答减少的发现一致。当将粘蛋白给予正常小鼠时，在与MZ B细胞相关的脾MZ中检测到一部分粘蛋白。此外，向正常小鼠施用粘蛋白明显减少了脾脏MZ B细胞，与荷瘤小鼠相似。这些结果表明，血液中的粘蛋白与CD 22相互作用，导致荷瘤状态下脾MZ B细胞受损。
CD22 [Siglec-2 (sialic acid-binding, immunoglobulin-like lectin-2)], a negative regulator of B-cell signalling, binds to alpha2,6- sialic acid-linked glycoconjugates, including a sialyl-Tn antigen that is one of the typical tumour-associated carbohydrate antigens expressed on various mucins. Many epithelial tumours secrete mucins into tissues and/or the bloodstream. Mouse mammary adenocarcinoma cells, TA3-Ha, produce a mucin named epiglycanin, but a subline of them, TA3-St, does not. Epiglycanin binds to CD22 and inhibits B-cell signalling in vitro. The in vivo effect of mucins in the tumour-bearing state was investigated using these cell lines. It should be noted that splenic MZ (marginal zone) B-cells were dramatically reduced in the mice bearing TA3-Ha cells but not in those bearing TA3-St cells, this being consistent with the finding that the thymus-independent response was reduced in these mice. When the mucins were administered to normal mice, a portion of them was detected in the splenic MZ associated with the MZ B-cells. Furthermore, administration of mucins to normal mice clearly reduced the splenic MZ B-cells, similar to tumour-bearing mice. These results indicate that mucins in the bloodstream interacted with CD22, which led to impairment of the splenic MZ B-cells in the tumour-bearing state.