Overexpression of branched O-linked oligosaccharides on T cell surface glycoproteins impairs humoral immune responses in transgenic mice.

Abstract

The aberrant expression of core 2 O-glycans on T cell surface glycoproteins has been associated with various immunodeficient syndromes such as Wiskott-Aldrich syndrome and AIDS. To determine the effect of this aberrant expression of core 2 O-glycans on immune responses, we previously generated transgenic mice overexpressing core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT) in T cells, and demonstrated that T cell primary immune responses mediated through interaction between T cells and antigen-presenting cells are impaired in the transgenic mice (Tsuboi, S., and Fukuda, M. (1997) EMBO J. 16, 6364-6373). In this study, we determined whether overexpression of core 2 oligosaccharides on T cells leads to impaired humoral immune responses by B cells using the same transgenic mice. When T cells were activated, both T and B cells from the transgenic and control mice expressed an equivalent amount of CD40L and CD40, which are, respectively, the receptor and counter-receptor for the interaction between T and B cells. However, activated T cells from the transgenic mice induced B cell proliferation less efficiently than those from control mice, regardless of whether B cells were isolated from control or the transgenic mice. This suggests that overexpression of core 2 O-glycans on T cell surface glycoproteins renders T cell-B cell interaction inefficient. Moreover, in the transgenic mice both immunoglobulin isotype switching and germinal center formation were also impaired. Taken together, these results indicate that aberrant expression of core 2 O-glycans on T cell surface glycoproteins results in impaired humoral immune responses due to an impaired interaction between T and B cells.

• Authors: S Tsuboi, M Fukuda
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 273 Issue 46 Pg. 30680-7 (Nov 13 1998) ISSN: 0021-9258 [Print] United States
• PMID: 9804842 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Membrane Glycoproteins
• Oligosaccharides
• CD40 Ligand
• N-Acetylglucosaminyltransferases
• beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,6-acetylglucosaminyl transferase

Topics

• Animals
• Antibody Formation
• B-Lymphocytes (immunology, metabolism)
• Blotting, Western
• CD40 Ligand
• CHO Cells
• Cricetinae
• Immunoglobulin Class Switching
• Lymphocyte Activation
• Membrane Glycoproteins
• Mice
• Mice, Transgenic
• N-Acetylglucosaminyltransferases (metabolism)
• Oligosaccharides (biosynthesis)
• T-Lymphocytes (immunology, metabolism)