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PMID: 9539767 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Immune regulation by the ST6Gal sialyltransferase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 8 ·1998-04-14 ·Pages 4504-9

Hennet T, Chui D, Paulson JC, Marth JD

Abstract

The ST6Gal sialyltransferase controls production of the Siaalpha2-6Galbeta1-4GlcNAc (Sia6LacNAc) trisaccharide, which is the ligand for the lectin CD22. Binding of CD22 to Sia6LacNAc is implicated in regulating lymphocyte adhesion and activation. We have investigated mice that lack ST6Gal and report that they are viable, yet exhibit hallmarks of severe immunosuppression unlike CD22-deficient mice. Notably, Sia6LacNAc-deficient mice display reduced serum IgM levels, impaired B cell proliferation in response to IgM and CD40 crosslinking, and attenuated antibody production to T-independent and T-dependent antigens. Deficiency of ST6Gal was further found to alter phosphotyrosine accumulation during signal transduction from the B lymphocyte antigen receptor. These studies reveal that the ST6Gal sialyltransferase and corresponding production of the Sia6LacNAc oligosaccharide are essential in promoting B lymphocyte activation and immune function.

MeSH Terms
Animals Antigens, CD/metabolism Antigens, Differentiation, B-Lymphocyte/metabolism B-Lymphocytes/immunology,metabolism Calcium/metabolism Carbohydrate Conformation Carbohydrate Sequence Cell Adhesion Molecules Cells, Cultured Chimera Cloning, Molecular Female Flow Cytometry Heterozygote Immunoglobulin A/blood Immunoglobulin G/blood Immunoglobulin M/blood Lectins Lymphocyte Activation Male Mice Mice, Inbred C57BL Molecular Sequence Data Mutagenesis, Site-Directed Phosphotyrosine/analysis Recombinant Proteins/immunology,metabolism Sialic Acid Binding Ig-like Lectin 2 Sialyltransferases/immunology,metabolism Trisaccharides/biosynthesis,chemistry
Chemicals
Antigens, CD Antigens, Differentiation, B-Lymphocyte Cd22 protein, mouse Cell Adhesion Molecules Immunoglobulin A Immunoglobulin G Immunoglobulin M Lectins Recombinant Proteins Sialic Acid Binding Ig-like Lectin 2 Trisaccharides Phosphotyrosine Sialyltransferases Calcium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hennet T
Howard Hughes Medical Institute, Division of Cellular and Molecular Medicine, and the Glycobiology Program, 9500 Gilman Drive 0625, University of California at San Diego, La Jolla, CA 92093, USA.
Chui D
Paulson J C
Marth J D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.8.4504
Published
1998-04-14
Pages
4504-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC22519
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.95.8.4504 PMC Full Text View journal details
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