Glycobiology Advance Access originally published online on October 2, 2007
Glycobiology 2008 18(1):114-124; doi:10.1093/glycob/cwm107
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Reduced
4β1 Integrin/VCAM-1 Interactions Lead to Impaired Pre-B Cell Repopulation in Alpha 1,6-Fucosyltransferase Deficient Mice
2 Departments of Glycotherapeutics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
3 Departments of Hematology and Oncology Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
4 Departments of Biochemistry, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
5 Department of Immunology and Molecular Genetics, Kawasaki Medical School, Okayama 701-0192, Japan
6 Takara Bio Inc. Shiga 520-2193, Japan
7 Department of Functional Diagnostic Science, Division of Health Science, Osaka University School of Health Sciences, Osaka 565-0871, Japan
8 Department of Disease Glycomics Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
1 To whom correspondence should be addressed: e-mail address: kondoa{at}glycot.med.osaka-u.ac.jp
Received on August 14, 2007; revised on September 21, 2007; accepted on September 27, 2007
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,
4β1 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+CD79blow 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.
Key words:
alpha 1,6-fucosyltransferase
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B-cell development
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CD45R; N-glycans
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4β1 integrin/VCAM-1