Reduced alpha 4 beta 1 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, alpha 4 beta 1 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.