Polylactosamine on glycoproteins influences basal levels of lymphocyte and macrophage activation

β1,3-N-acetylglucosaminyltransferase 2 (β3GnT2) is a polylactosamine synthase that synthesizes a backbone structure of carbohydrate structures onto glycoproteins. Here we generated β3GnT2-deficient (β3GnT2⁻/⁻) mice and showed that polylactosamine on N-glycans was markedly reduced in their immunologi...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2007-10, Vol.104 (40), p.15829-15834
Main Authors: Togayachi, Akira, Kozono, Yuko, Ishida, Hiroyasu, Abe, Sumie, Suzuki, Nami, Tsunoda, Yuki, Hagiwara, Kozue, Kuno, Atsushi, Ohkura, Takashi, Sato, Nobuo, Sato, Takashi, Hirabayashi, Jun, Ikehara, Yuzuru, Tachibana, Kouichi, Narimatsu, Hisashi
Format: Article
Language:English
Subjects:
Amino Sugars - deficiency
Animals
Antibodies
Antigens, CD19 - immunology
B lymphocytes
Biological Sciences
CD28 Antigens - immunology
Cell lines
Cellular biology
Glycoproteins
Immune system
Lectins
Lycopersicon esculentum
Lymphocyte Activation - genetics
Lymphocytes
Macrophage Activation - genetics
Macrophages
Mice
Mice, Knockout
Molecules
N-Acetylglucosaminyltransferases - deficiency
Physiological regulation
Plant Lectins - immunology
Polysaccharides
Polysaccharides - deficiency
Receptors, Antigen, T-Cell - immunology
Rodents
T lymphocytes
T-Lymphocytes - immunology
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Summary:β1,3-N-acetylglucosaminyltransferase 2 (β3GnT2) is a polylactosamine synthase that synthesizes a backbone structure of carbohydrate structures onto glycoproteins. Here we generated β3GnT2-deficient (β3GnT2⁻/⁻) mice and showed that polylactosamine on N-glycans was markedly reduced in their immunological tissues. In WT mice, polylactosamine was present on CD28 and CD19, both known immune costimulatory molecules. However, polylactosamine levels on these molecules were reduced in β3GnT2⁻/⁻ mice. β3GnT2⁻/⁻ T cells lacking polylactosamine were more sensitive to the induction of intracellular calcium flux on stimulation with anti-CD3ε/CD28 and proliferated more strongly than T cells from WT mice. β3GnT2⁻/⁻ B cells also showed hyperproliferation on BCR stimulation. Macrophages from β3GnT2⁻/⁻ mice had higher cell surface CD14 levels and enhanced responses to endotoxin. These results indicate that polylactosamine on N-glycans is a putative immune regulatory factor presumably suppressing excessive responses during immune reactions.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0707426104