Immune regulation by the ST6Gal sialyltransferase.
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.
Hennet
T
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
D
Paulson
J C
JC
Marth
J D
JD
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D002678:Chimera; D003001:Cloning, Molecular; D005260:Female; D005434:Flow Cytometry; D006579:Heterozygote; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D037102:Lectins; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019000:Phosphotyrosine / Q000032:analysis; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2; D012799:Sialyltransferases / Q000276:immunology / Q000378:metabolism*; D014312:Trisaccharides / Q000096:biosynthesis / Q000737:chemistry
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D037102:Lectins; D011994:Recombinant Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2; D014312:Trisaccharides; D019000:Phosphotyrosine; D012799:Sialyltransferases; D002118:Calcium