Synthetic glycan ligand excludes CD22 from antigen receptor-containing lipid rafts.
CD22/Siglec-2 is a B cell membrane-bound lectin that recognizes glycan ligands containing alpha2,6-linked sialic acid, and negatively regulates signaling through the B cell antigen receptor (BCR). Previous studies demonstrated that synthetic sialosides that bind to CD22 augment BCR signaling by inhibiting CD22-mediated BCR regulation. Here we demonstrate that, after antigen stimulation, CD22 forms a cap together with BCR, and translocates to lipid rafts. Both co-capping of CD22 with BCR and translocation of CD22 to lipid rafts were markedly blocked by a synthetic alpha2,6-linked sialic acid, Neu5Gcalpha2-6GalbetaSE. These results strongly suggest that synthetic glycan ligand excludes CD22 from BCR-containing lipid rafts. Because CD22-mediated signal regulation requires phosphorylation of CD22 by Lyn that localizes in lipid rafts and is activated by BCR, synthetic glycan ligand regulates localization of CD22 crucial for signal regulation.
Yu
Jie
J
Laboratory of Immunology, School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Sawada
Toshihiko
T
Adachi
Takahiro
T
Gao
Xiaoming
X
Takematsu
Hiromu
H
Kozutsumi
Yasunori
Y
Ishida
Hideharu
H
Kiso
Makoto
M
Tsubata
Takeshi
T
D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D015153:Blotting, Western; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D008024:Ligands; D050356:Lipid Metabolism; D051379:Mice; D011134:Polysaccharides / Q000378:metabolism*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000378:metabolism*
D017931:DNA Primers; D008024:Ligands; D011134:Polysaccharides; D051918:Sialic Acid Binding Ig-like Lectin 2