Down-modulation of B cell signal transduction by ligation of mucins to CD22.
Epithelial cancer cells secrete mucins carrying carbohydrate antigens such as a sialyl-Tn antigen into cancer tissues and/or the bloodstream, in which mucins may interact with CD22 (Siglec-2). Mucins isolated from colon cancer cells and bovine submaxillary mucins bound to CD22 cDNA transfectants and a human B cell line, Daudi cell, and the binding of soluble recombinant CD22 to the mucins was confirmed by means of a plate assay. The binding specificity was demonstrated by the fact that the mucins bound to the recombinant CD22 with an intact ectodomain but not to that with a mutated ectodomain. Daudi cells were stimulated with anti-IgM F(ab')(2) in the presence or absence of mucins. Ligation of mucins to CD22 decreased the phosphorylation of CD22 and SHP-1 recruitment, and the phosphorylation of ERK-1/2 prominently. The in vivo effect of mucins on splenic B cells in the tumor-bearing state was investigated using mucin-producing (TA3-Ha) and non-producing (TA3-St) mammary adenocarcinoma-bearing mice. When fluorescence-labeled epiglycanins were administered to normal mice, a portion of them was taken up by the spleen and became associated with splenic B cells. We found that splenic B cells were reduced in TA3-Ha-bearing mice but not in TA3-St-bearing ones. These results suggest that in the tumor-bearing state a portion of the mucins in the bloodstream was taken up by the spleen and ligated to CD22 expressed on splenic B cells, which may have led to down-regulation of signal transduction.
Toda
Munetoyo
M
Department of Biotechnology, Faculty of Engineering, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan.
Akita
Kaoru
K
Inoue
Mizue
M
Taketani
Shigeru
S
Nakada
Hiroshi
H
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002417:Cattle; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology*; D015536:Down-Regulation; D006801:Humans; D007108:Immune Tolerance; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009077:Mucins / Q000378:metabolism*; D010766:Phosphorylation; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology
D007140:Immunoglobulin Fab Fragments; D007075:Immunoglobulin M; D009077:Mucins; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6