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

J Biol Chem. 1998 Nov 13;273(46):30680-7. doi: 10.1074/jbc.273.46.30680.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibody Formation
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / 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*
  • T-Lymphocytes / metabolism


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