title: Foxo1 regulates marginal zone B-cell development.
abstract: A fundamental component of signaling initiated by the BCR and CD19 is the activation of phosphoinositide 3-kinase. Downstream of phosphoinositide 3-kinase, the protein kinase AKT phosphorylates several substrates, including members of the forkhead box subgroup O (Foxo) transcription factor family. Among the Foxo proteins, Foxo1 has unique functions in bone marrow B-cell development and peripheral B-cell function. Here, we report a previously unrecognized role for Foxo1 in controlling the ratio of mature B-cell subsets in the spleen. Conditional deletion of Foxo1 in B cells resulted in an increased percentage of marginal zone B cells and a decrease in follicular (FO) B cells. In addition, Foxo1 deficiency corrected the absence of marginal zone B cells that occurs in CD19-deficient mice. These findings show that Foxo1 regulates the balance of mature B-cell subsets and is required for the marginal zone B-cell deficiency phenotype of mice lacking CD19.
authors.affiliation: Department of Molecular Biology & Biochemistry, Institute for Immunology, University of California Irvine, Irvine, CA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Limon
authors.forename: Caroline
authors.initials: C
authors.lastname: Blanc
authors.forename: Stanford L
authors.initials: SL
authors.lastname: Peng
authors.forename: David A
authors.initials: DA
authors.lastname: Fruman
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013154:Spleen / Q000196:embryology / Q000276:immunology* / Q000473:pathology
chemical_list: D018941:Antigens, CD19; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse
references.citation: Immunol Res. 2002;26(1-3):45-54
references.pmid: 12403344
references.citation: Nat Immunol. 2008 Dec;9(12):1388-98
references.pmid: 18978794
references.citation: Blood. 2010 May 20;115(20):4043-50
references.pmid: 20042722
references.citation: J Immunol. 2009 Jun 15;182(12):7343-7
references.pmid: 19494255
references.citation: J Immunol. 2006 Mar 1;176(5):2711-21
references.pmid: 16493026
references.citation: Oncogene. 2008 Apr 7;27(16):2289-99
references.pmid: 18391971
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12747-52
references.pmid: 16908841
references.citation: Cell. 2004 Apr 16;117(2):211-23
references.pmid: 15084259
references.citation: Eur J Immunol. 2007 Oct;37(10):2923-36
references.pmid: 17724683
references.citation: Int Immunol. 2008 May;20(5):671-81
references.pmid: 18375530
references.citation: Nat Immunol. 2008 May;9(5):513-21
references.pmid: 18391955
references.citation: J Immunol. 2006 Feb 15;176(4):2389-96
references.pmid: 16455997
references.citation: Semin Cell Dev Biol. 2004 Apr;15(2):183-97
references.pmid: 15209378
references.citation: Int Immunol. 2004 Dec;16(12):1789-98
references.pmid: 15520044
references.citation: Immunity. 2009 Mar 20;30(3):358-71
references.pmid: 19285438
references.citation: Autoimmunity. 2009 Aug;42(5):447-58
references.pmid: 19811262
references.citation: J Exp Med. 1999 Jul 5;190(1):75-89
references.pmid: 10429672
references.citation: Nat Immunol. 2003 Mar;4(3):280-6
references.pmid: 12563258
references.citation: Immunol Res. 2005;31(2):119-31
references.pmid: 15778510
references.citation: Nat Immunol. 2009 Feb;10(2):176-84
references.pmid: 19136962
references.citation: J Exp Med. 2002 Sep 16;196(6):753-63
references.pmid: 12235209
references.citation: J Immunol. 2008 Sep 1;181(5):2980-9
references.pmid: 18713968
references.citation: Immunol Rev. 2009 Mar;228(1):253-72
references.pmid: 19290933
references.citation: Immunity. 2002 Oct;17(4):501-14
references.pmid: 12387743
references.citation: Nature. 2006 Jul 20;442(7100):299-302
references.pmid: 16855590
references.citation: Nucleic Acids Res. 1997 Mar 15;25(6):1317-8
references.pmid: 9092650
references.citation: Oncogene. 2008 Apr 7;27(16):2337-44
references.pmid: 18391975
references.citation: Nat Immunol. 2003 Mar;4(3):287-94
references.pmid: 12563260
references.citation: Eur J Immunol. 1997 Sep;27(9):2366-74
references.pmid: 9341782
references.citation: Annu Rev Immunol. 2006;24:99-146
references.pmid: 16551245
references.citation: Nat Immunol. 2008 Mar;9(3):292-300
references.pmid: 18246069
references.citation: Eur J Immunol. 2009 Nov;39(11):2991-9
references.pmid: 19658095
references.citation: Nat Immunol. 2008 Jan;9(1):63-72
references.pmid: 18059271
references.citation: Curr Opin Immunol. 2008 Apr;20(2):149-57
references.pmid: 18434123
references.citation: Immunity. 2005 Sep;23(3):297-308
references.pmid: 16169502