CD22 [Siglec-2 (sialic acid-binding, immunoglobulin-like lectin-2)], a negative regulator of B-cell signalling, binds to α2,6- 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.
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Research Article|
January 16 2009
Ligation of tumour-produced mucins to CD22 dramatically impairs splenic marginal zone B-cells
Munetoyo Toda;
Munetoyo Toda
*Department of Biotechnology, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan
†CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan
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Risa Hisano;
Risa Hisano
*Department of Biotechnology, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan
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Hajime Yurugi;
Hajime Yurugi
*Department of Biotechnology, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan
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Kaoru Akita;
Kaoru Akita
*Department of Biotechnology, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan
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Kouji Maruyama;
Kouji Maruyama
*Department of Biotechnology, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan
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Mizue Inoue;
Mizue Inoue
*Department of Biotechnology, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan
†CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan
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Takahiro Adachi;
Takahiro Adachi
†CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan
‡Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
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Takeshi Tsubata;
Takeshi Tsubata
†CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan
‡Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
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Hiroshi Nakada
Hiroshi Nakada
1
*Department of Biotechnology, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan
†CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan
1To whom correspondence should be addressed (email hnakada@cc.kyoto-su.ac.jp).
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Publisher: Portland Press Ltd
Received:
June 17 2008
Revision Received:
September 05 2008
Accepted:
October 17 2008
Accepted Manuscript online:
October 17 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 417 (3): 673–683.
Article history
Received:
June 17 2008
Revision Received:
September 05 2008
Accepted:
October 17 2008
Accepted Manuscript online:
October 17 2008
Citation
Munetoyo Toda, Risa Hisano, Hajime Yurugi, Kaoru Akita, Kouji Maruyama, Mizue Inoue, Takahiro Adachi, Takeshi Tsubata, Hiroshi Nakada; Ligation of tumour-produced mucins to CD22 dramatically impairs splenic marginal zone B-cells. Biochem J 1 February 2009; 417 (3): 673–683. doi: https://doi.org/10.1042/BJ20081241
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