Glycobiology Advance Access published online on October 2, 2007
Glycobiology, doi:10.1093/glycob/cwm107
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Reduced
4ß1 integrin /VCAM-1 Interactions Lead to Impaired Pre-B Cell Repopulation in Alpha 1,6-Fucosyltransferase Deficient Mice
2 Department of Glycotherapeutics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
3 Department of Immunology and Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan
4 Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
5 Takara Bio Inc., Shiga 520-2193, Japan
6 Department of Biochemistry, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
7 Department of Functional Diagnostic Science , Division of Health Science, Osaka University School of Health Sciences
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: kondoa{at}glycot.med.osaka-u.ac.jp
Received on August 14, 2007; accepted on September 27, 2007
Mice with a targeted gene disruption of the 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,
4ß1 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 down-regulated 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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4ß1 integrin/VCAM-1
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N-glycans
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CD45R