title: Reduced alpha4beta1 integrin/VCAM-1 interactions lead to impaired pre-B cell repopulation in alpha 1,6-fucosyltransferase deficient mice.
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.
authors.affiliation: Department of Glycotherapeutics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Li
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ishihara
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yokota
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Nobuto
authors.initials: N
authors.lastname: Koyama
authors.forename: Jinhua
authors.initials: J
authors.lastname: Jin
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mizuno-Horikawa
authors.forename: Xiangchun
authors.initials: X
authors.lastname: Wang
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kondo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005643:Fucose / Q000378:metabolism; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D017154:Stromal Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1; D005643:Fucose; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase