Notch2 regulates the development of marginal zone B cells through Fos

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• 作者：Shuichi Iwahashi^a ; ^b ; Yoichi Maekawa^a ; Jun Nishida^a ; Chieko Ishifune^a ; Akiko Kitamura^a ; Hideki Arimochi^a ; Keiko Kataoka^a ; Shigeru Chiba^c ; Mitsuo Shimada^b ; Koji Yasutomo^a ; ^{yasutomo@basic.med.tokushima-u.ac.jp}
• 关键词：Notch ; Fos ; Marginal zone B cells
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：24 February, 2012
• 卷：418
• 期：4
• 页码：701-707
• 文件大小：868 K

摘要

B cells are classified into several subsets depending on their functions, marker expression pattern and localization. Marginal zone B (MZB) cells are a distinct lineage from follicular B cells, and regulate host defenses against blood-borne pathogens. Notch2/RBP-J signaling regulates the development of MZB cells by interacting with delta-like 1 ligand, although the target genes for Notch2 signaling remain unclear. We identified Fos as an upregulated gene in LPS-stimulated B cells that received Notch2 signaling. Fos is expressed in CD21^highCD23^low MZB cells at a higher level compared to CD21^IntCD23^high follicular B cells. Deleting the Notch2 gene in CD19⁺ B cells decreased Fos expression in B cells. Overexpression of Fos in Notch2-deficient B cells or bone marrow cells partially restored MZB development. Fos promoter activity was upregulated by Notch2 signaling, indicating that Notch2 directly controls Fos transcription associated with MZB development. These data identify Fos as one of the target genes for Notch2 signaling that is crucial for MZB development.