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Foxo1 regulates marginal zone B-cell development

✍ Scribed by Jing Chen; Jose J. Limon; Caroline Blanc; Stanford L. Peng; David A. Fruman

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
345 KB
Volume
40
Category
Article
ISSN
0014-2980

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✦ Synopsis

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.

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