Reduced alpha4beta1 integrin/VCAM-1 interactions lead to impaired pre-B cell repopulation in alpha 1,6-fucosyltransferase deficient mice.
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.
Li
Wenzhe
W
Department of Glycotherapeutics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
Ishihara
Katsuhiko
K
Yokota
Takafumi
T
Nakagawa
Takatoshi
T
Koyama
Nobuto
N
Jin
Jinhua
J
Mizuno-Horikawa
Yoko
Y
Wang
Xiangchun
X
Miyoshi
Eiji
E
Taniguchi
Naoyuki
N
Kondo
Akihiro
A
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*
D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1; D005643:Fucose; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase