IMMUNE REGULATION BY THE ST6GAL SIALYLTRANSFERASE

The ST6Gal sialyltransferase controls production of the Sia alpha 2-6G al beta 1-4GlcNAc (Sia6LacNAc) trisaccharide, which is the ligand for the lectin CD22. Binding of CD22 to Sia6GLacNAc is implicated in regul ating lymphocyte adhesion and activation. We have investigated mice th at lack ST6Gal and report that they are viable, yet exhibit hallmarks of severe immunosuppression unlike CD22-deficient mice. Notably, Sia6L acNAc-deficient mice display reduced serum IgM levels, impaired B cell proliferation in response to IgM and CD40 crosslinking, and attenuate d antibody production to T-independent and T-dependent antigens. Defic iency of ST6Gal was further found to alter phosphotyrosine accumulatio n during signal transduction from the B lymphocyte antigen receptor. T hese studies reveal that the ST6Gal sialyltransferase and correspondin g production of the Sia6LacNAc oligosaccharide are essential in promot ing B lymphocyte activation and immune function.