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PMID: 20449867 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Foxo1 regulates marginal zone B-cell development.

European journal of immunology ·Vol. 40 ·No. 7 ·2010-07-00 ·Pages 1890-6

Chen J, Limon JJ, Blanc C, Peng SL, Fruman DA

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.

MeSH Terms
Animals Antigens, CD19/genetics,immunology,metabolism B-Lymphocytes/immunology,metabolism,pathology Cell Differentiation Cell Proliferation Cell Separation Cells, Cultured Flow Cytometry Forkhead Box Protein O1 Forkhead Transcription Factors/genetics,immunology,metabolism Gene Expression Regulation, Developmental/immunology Immunoglobulin Class Switching/genetics Mice Mice, Knockout Precursor Cells, B-Lymphoid/immunology,metabolism,pathology Spleen/embryology,immunology,pathology
Chemicals
Antigens, CD19 Forkhead Box Protein O1 Forkhead Transcription Factors Foxo1 protein, mouse
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chen Jing
Department of Molecular Biology & Biochemistry, Institute for Immunology, University of California Irvine, Irvine, CA, USA.
Limon Jose J
Blanc Caroline
Peng Stanford L
Fruman David A
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Article Info
Journal
European journal of immunology
Abbr.
Eur J Immunol
ISSN
1521-4141
DOI
10.1002/eji.200939817
Published
2010-07-00
Pages
1890-6
Language
English
Region
Germany
NLM ID
1273201
PMCID
PMC2926184
Subset
IM
Grants
NIAID NIH HHS · R01 AI057471 · United States
NIAID NIH HHS · AI057471 · United States
NIAID NIH HHS · R01 AI061478 · United States
NCI NIH HHS · P30 CA062203 · United States
NIAID NIH HHS · R01 AI057471-01 · United States
NIAID NIH HHS · R01 AI061478-01 · United States
NIAID NIH HHS · AI061478 · United States
External Links
PubMed source DOI: 10.1002/eji.200939817 PMC Full Text View journal details
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