title: Notch2 regulates the development of marginal zone B cells through Fos.
abstract: 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(high)CD23(low) MZB cells at a higher level compared to CD21(Int)CD23(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.
authors.affiliation: Department of Immunology and Parasitology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Iwahashi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Maekawa
authors.forename: Jun
authors.initials: J
authors.lastname: Nishida
authors.forename: Chieko
authors.initials: C
authors.lastname: Ishifune
authors.forename: Akiko
authors.initials: A
authors.lastname: Kitamura
authors.forename: Hideki
authors.initials: H
authors.lastname: Arimochi
authors.forename: Keiko
authors.initials: K
authors.lastname: Kataoka
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.forename: Koji
authors.initials: K
authors.lastname: Yasutomo
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D016761:Oncogene Proteins v-fos / Q000235:genetics*; D011401:Promoter Regions, Genetic; D051883:Receptor, Notch2 / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D014158:Transcription, Genetic
chemical_list: C497765:Notch2 protein, mouse; D016761:Oncogene Proteins v-fos; D051883:Receptor, Notch2; D008156:Luciferases