Reduced alpha4beta1 integrin/VCAM-1 interactions lead to impaired pre-B cell repopulation in alpha 1,6-fucosyltransferase deficient mice

Glycobiology. 2008 Jan;18(1):114-24. doi: 10.1093/glycob/cwm107. Epub 2007 Oct 2.

Abstract

Mice with a targeted gene disruption of Fut8 (Fut8(-/-)) showed an abnormality in the transition from pro-B cell to pre-B cell, reduced peripheral B cells, and a decreased immunoglobulin production. Alpha 1,6-fucosyltransferase (FUT8) is responsible for the alpha 1,6 core fucosylation of N-glycans, which could modify the functions of glycoproteins. The loss of a core fucose in both very late antigen 4 (VLA-4, alpha4beta1 integrin) and vascular cell adhesion molecule 1 (VCAM-1) led to a decreased binding between pre-B cells and stromal cells, which impaired pre-B cells generation in Fut8(-/-) mice. Moreover, the B lineage genes, such as CD79a, CD79b, Ebf1, and Tcfe2a, were downregulated in Fut8(-/-) pre-B cells. Indeed, the frequency of preBCR(+)CD79b(low) cells in bone marrow pre-B cells in Fut8(-/-) was much lower than that in Fut8(+/+) cells. These results reveal a new role of core fucosylated N-glycans in mediating early B cell development and functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Fucose / metabolism
  • Fucosyltransferases / genetics
  • Fucosyltransferases / metabolism
  • Fucosyltransferases / physiology*
  • Integrin alpha4beta1 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Precursor Cells, B-Lymphoid / cytology*
  • Precursor Cells, B-Lymphoid / enzymology
  • Precursor Cells, B-Lymphoid / metabolism
  • Stromal Cells
  • Vascular Cell Adhesion Molecule-1 / metabolism*

Substances

  • Integrin alpha4beta1
  • Vascular Cell Adhesion Molecule-1
  • Fucose
  • Fucosyltransferases
  • Glycoprotein 6-alpha-L-fucosyltransferase