Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells
Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells
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DOI：
10.1038/ni793
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发表时间：
2002-05-01
影响因子：
30.5
通讯作者：
Honjo, T
中科院分区：
文献类型：
--
作者：
Tanigakik, K;Han, H;Honjo, T
RBP-J 是 Notch 信号传导的关键介质，可调节不同谱系的细胞命运决定。为了研究Notch-RBP-J在成熟B细胞分化中的功能，我们使用条件诱变产生了选择性缺乏B细胞RBP-J表达的小鼠。 RBP-J 的缺失导致边缘区 B (MZB) 细胞的损失，同时滤泡 B 细胞的增加；相反，腹膜腔中的 B I 细胞未受影响。 RBP-J 的缺乏不会导致 B 细胞维持、存活、浆细胞分化或激活方面的缺陷。因此，Notch-RBP-J 信号传导可能调节成熟 B 细胞向滤泡细胞与 MZB 细胞的谱系定型。此外，在 RBP-J 缺陷的 B 细胞小鼠中，聚蔗糖、脂多糖或鸡丙种球蛋白对免疫球蛋白的产生没有明显的变化。相比之下，这些小鼠在血源性细菌感染后死亡率增加，这表明 MZB 细胞在清除这些细菌中发挥着关键作用。
RBP-J is a key mediator of Notch signaling that regulates cell fate determination in various lineages. To investigate the function of Notch-RBP-J in mature B cell differentiation, we generated mice that selectively lacked B cell RBP-J expression using conditional mutagenesis. Absence of RBP-J led to the loss of marginal zone B (MZB) cells with a concomitant increase in follicular B cells; in contrast, B I cells in the peritoneal cavity were unaffected. Lack of RBP-J caused no defects in B cells maintenance, survival, plasma cell differentiation or activation. It is therefore likely that Notch-RBP-J signaling regulates the lineage commitment of mature B cells into follicular versus MZB cells. In addition, in mice with RBP-J-deficient B cells, had no obvious changes in immunoglobulin production in response to Ficoll, lipopolysaccharide or chicken gammaglobulin. In contrast, these mice exhibited increased mortality rates after blood-borne bacterial infection, which indicates that MZB cells play pivotal roles in the clearance of these bacteria.