Foxo1 regulates marginal zone B-cell development.
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.
Chen
Jing
J
Department of Molecular Biology & Biochemistry, Institute for Immunology, University of California Irvine, Irvine, CA, USA.
Limon
Jose J
JJ
Blanc
Caroline
C
Peng
Stanford L
SL
Fruman
David A
DA
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
D018941:Antigens, CD19; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse
Immunol Res. 2002;26(1-3):45-54
12403344
Nat Immunol. 2008 Dec;9(12):1388-98
18978794
Blood. 2010 May 20;115(20):4043-50
20042722
J Immunol. 2009 Jun 15;182(12):7343-7
19494255
J Immunol. 2006 Mar 1;176(5):2711-21
16493026
Oncogene. 2008 Apr 7;27(16):2289-99
18391971
Proc Natl Acad Sci U S A. 2006 Aug 22;103(34):12747-52
16908841
Cell. 2004 Apr 16;117(2):211-23
15084259
Eur J Immunol. 2007 Oct;37(10):2923-36
17724683
Int Immunol. 2008 May;20(5):671-81
18375530
Nat Immunol. 2008 May;9(5):513-21
18391955
J Immunol. 2006 Feb 15;176(4):2389-96
16455997
Semin Cell Dev Biol. 2004 Apr;15(2):183-97
15209378
Int Immunol. 2004 Dec;16(12):1789-98
15520044
Immunity. 2009 Mar 20;30(3):358-71
19285438
Autoimmunity. 2009 Aug;42(5):447-58
19811262
J Exp Med. 1999 Jul 5;190(1):75-89
10429672
Nat Immunol. 2003 Mar;4(3):280-6
12563258
Immunol Res. 2005;31(2):119-31
15778510
Nat Immunol. 2009 Feb;10(2):176-84
19136962
J Exp Med. 2002 Sep 16;196(6):753-63
12235209
J Immunol. 2008 Sep 1;181(5):2980-9
18713968
Immunol Rev. 2009 Mar;228(1):253-72
19290933
Immunity. 2002 Oct;17(4):501-14
12387743
Nature. 2006 Jul 20;442(7100):299-302
16855590
Nucleic Acids Res. 1997 Mar 15;25(6):1317-8
9092650
Oncogene. 2008 Apr 7;27(16):2337-44
18391975
Nat Immunol. 2003 Mar;4(3):287-94
12563260
Eur J Immunol. 1997 Sep;27(9):2366-74
9341782
Annu Rev Immunol. 2006;24:99-146
16551245
Nat Immunol. 2008 Mar;9(3):292-300
18246069
Eur J Immunol. 2009 Nov;39(11):2991-9
19658095
Nat Immunol. 2008 Jan;9(1):63-72
18059271
Curr Opin Immunol. 2008 Apr;20(2):149-57
18434123
Immunity. 2005 Sep;23(3):297-308
16169502