Toda Munetoyo, Hisano Risa, Yurugi Hajime, Akita Kaoru, Maruyama Kouji, Inoue Mizue, Adachi Takahiro, Tsubata Takeshi, Nakada Hiroshi
Department of Biotechnology, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan.
Biochem J. 2009 Feb 1;417(3):673-83. doi: 10.1042/BJ20081241.
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.
CD22 [唾液酸结合性免疫球蛋白样凝集素-2（Siglec-2）] 是B细胞信号传导的负调节因子，可与α2,6-唾液酸连接的糖缀合物结合，包括一种唾液酸化Tn抗原，它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。许多上皮肿瘤会将粘蛋白分泌到组织和/或血液中。小鼠乳腺腺癌细胞TA3-Ha可产生一种名为表聚糖的粘蛋白，但其亚系TA3-St则不会。表聚糖可与CD22结合并在体外抑制B细胞信号传导。利用这些细胞系研究了肿瘤状态下粘蛋白的体内作用。需要注意的是，携带TA3-Ha细胞的小鼠脾脏边缘区（MZ）B细胞显著减少，而携带TA3-St细胞的小鼠则没有，这与这些小鼠中胸腺非依赖性反应降低的发现一致。当将粘蛋白给予正常小鼠时，其中一部分在与MZ B细胞相关的脾脏MZ中被检测到。此外，给正常小鼠注射粘蛋白明显减少了脾脏MZ B细胞，类似于荷瘤小鼠。这些结果表明，血液中的粘蛋白与CD22相互作用，导致荷瘤状态下脾脏MZ B细胞受损。
