Core fucosylation of IgG B cell receptor is required for antigen recognition and antibody production

J Immunol. 2015 Mar 15;194(6):2596-606. doi: 10.4049/jimmunol.1402678. Epub 2015 Feb 18.

Abstract

Ag recognition and Ab production in B cells are major components of the humoral immune response. In the current study, we found that the core fucosylation catalyzed by α1,6-fucosyltransferase (Fut8) was required for the Ag recognition of BCR and the subsequent signal transduction. Moreover, compared with the 3-83 B cells, the coalescing of lipid rafts and Ag-BCR endocytosis were substantially reduced in Fut8-knockdown (3-83-KD) cells with p31 stimulation and then completely restored by reintroduction of the Fut8 gene to the 3-83-KD cells. Indeed, Fut8-null (Fut8(-/-)) mice evoked a low immune response following OVA immunization. Also, the frequency of IgG-producing cells was significantly reduced in the Fut8(-/-) spleen following OVA immunization. Our results clearly suggest an unexpected mode of BCR function, in which the core fucosylation of IgG-BCR mediates Ag recognition and, concomitantly, cell signal transduction via BCR and Ab production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibody Formation / immunology*
  • Antigens / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Base Sequence
  • Binding Sites / genetics
  • Blotting, Western
  • Cells, Cultured
  • Endocytosis / immunology
  • Flow Cytometry
  • Fucose / immunology
  • Fucose / metabolism
  • Fucosyltransferases / deficiency
  • Fucosyltransferases / genetics
  • Fucosyltransferases / immunology
  • Glycosylation
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / metabolism
  • Membrane Microdomains / immunology
  • Membrane Microdomains / metabolism
  • Mice, Inbred ICR
  • Mice, Knockout
  • Molecular Sequence Data
  • Ovalbumin / immunology
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction / immunology
  • Spleen / immunology
  • Spleen / metabolism

Substances

  • Antigens
  • Immunoglobulin G
  • Receptors, Antigen, B-Cell
  • Fucose
  • Ovalbumin
  • Fucosyltransferases
  • Glycoprotein 6-alpha-L-fucosyltransferase