Reduced alpha4beta1 integrin/VCAM-1 interactions lead to impaired pre-B cell repopulation in alpha 1,6-fucosyltransferase deficient mice.
Reduced alpha4beta1 integrin/VCAM-1 interactions lead to impaired pre-B cell repopulation in alpha 1,6-fucosyltransferase deficient mice.
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发表时间：
2008
期刊：
影响因子：
4.3
通讯作者：
Wenzhe Li;K. Ishihara;T. Yokota;T. Nakagawa;N. Koyama;Jinhua Jin;Y. Mizuno-Horikawa;Xiangchun E. Wang;E. Miyoshi;N. Taniguchi;A. Kondo
中科院分区：
文献类型：
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作者：
Wenzhe Li;K. Ishihara;T. Yokota;T. Nakagawa;N. Koyama;Jinhua Jin;Y. Mizuno-Horikawa;Xiangchun E. Wang;E. Miyoshi;N. Taniguchi;A. Kondo
带有Fut8(-/-)靶向基因中断的小鼠表现出从前B细胞到前B细胞的转变异常，外周B细胞减少，免疫球蛋白产生减少。α-1，6-岩藻糖基转移酶(FUT8)负责N-糖链的α-1，6核心岩藻糖基化，可修饰糖蛋白的功能。极晚期抗原4(VLA-4，α4beta1整合素)和血管细胞黏附分子1(VCAM-1)中核心岩藻糖的缺失导致前B细胞与基质细胞结合减少，从而影响Fut8(-/-)小鼠前B细胞的生成。此外，CD79a、CD79b、EBF1和Tcfe2a等B系基因在Fut8(-/-)前B细胞中表达下调。事实上，在Fut8(-/-)骨髓前B细胞中，前BCR(+)CD79b(低)细胞的频率远低于Fut8(+/+)细胞。这些结果揭示了核心岩藻糖化N-糖链在调节早期B细胞发育和功能中的新作用。
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.