Human B-lymphocytes express alpha2-6-sialylated 6-sulfo-N-acetyllactosamine serving as a preferred ligand for CD22/Siglec-2.
CD22/Siglec-2, an important inhibitory co-receptor on B-lymphocytes, is known to recognize alpha2-6-sialylated glycan as a specific ligand. Here we propose that the alpha2-6-sialylated and 6-GlcNAc-sulfated determinant serves as a preferred ligand for CD22 because the binding of a human B-cell line to CD22 was almost completely abrogated after incubating the cells with NaClO3, an inhibitor of cellular sulfate metabolism, and was also significantly inhibited by a newly generated monoclonal antibody specific to the alpha2-6-sialylated 6-sulfo-N-acetyllactosamine (LacNAc) determinant (KN343, murine IgM). The alpha2-6-sialylated 6-sulfo-LacNAc determinant defined by the antibody was significantly expressed on a majority of normal human peripheral B-lymphocytes as well as follicular B-lymphocytes in peripheral lymph nodes. The determinant was also expressed in endothelial cells of high endothelial venules of secondary lymphoid tissues, including lymph nodes, tonsils, and intestine-associated lymphoid tissues, more strongly than on B-lymphocytes, suggesting a role for CD22 in B-cell interaction with blood vessels and trafficking. These results indicate that the alpha2-6-sialylated 6-sulfo-LacNAc determinant serves as an endogenous ligand for human CD22 and suggest the possibility that 6-GlcNAc sulfation as well as alpha2-6-sialylation may regulate CD22/Siglec-2 functions in humans.
Kimura
Naoko
N
Department of Molecular Pathology, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
Ohmori
Katsuyuki
K
Miyazaki
Keiko
K
Izawa
Mineko
M
Matsuzaki
Yuji
Y
Yasuda
Yosuke
Y
Takematsu
Hiromu
H
Kozutsumi
Yasunori
Y
Moriyama
Akihiko
A
Kannagi
Reiji
R
D000606:Amino Sugars / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D006801:Humans; D008024:Ligands; D008221:Lymphoid Tissue / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000378:metabolism*
C467438:6-sulfo-LacNac; D000606:Amino Sugars; D000911:Antibodies, Monoclonal; D008024:Ligands; D051918:Sialic Acid Binding Ig-like Lectin 2