Impaired pre-B cell development in the alpha 1,6-fucosyltransferase deficient mice (83.13)

Abstract The alpha 1,6-fucosyltransferase (FUT8) is responsible for the core-fucosylation of N-glycans and core fucose of N-glycans could modify function of glycoproteins on the cell surface. Mice with a targeted gene disruption of Fut8 (Fut8−/−) had impaired B cell development at the pre-B cell stage, reduced numbers of immature B cells, reduced B cell proliferative responses and antibody production. Our finding for the first time showed impaired early B cells development owing to the low binding affinity of VLA-4 to VCAM-1 in Fut8-KD-pre-B cells. Consistently, reintroduction of Fut8 partly restored the binding affinity by an increase in the percentage of binding cells from 29% to 44%, indicating that core fucosylation is required for VLA-4/VCAM-1 interaction during B cell development. Loss of early B cell lineage was associated with down-regulation of several gene expressions, such as CD79a, CD79b, Ebf1, Tcfe2a in Fut8−/− CD45R+IgM− cells. Indeed, the ratio of pre-BCR+CD79b+ cells in gated Fut8−/− pre-B cells was much lower than in Fut8+/+ pre-B cells, indicating a differentiation defect in the transition from pro-B cell to pre-B cell. These results provide evidence that Fut8 is functionally linked to the VLA-4/VCAM-1 interaction in mediating B cell tethering to stromal cells and is pivotal in B cell development and activation.