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PI3 kinase and FOXO1 transcription factor activity differentially control B cells in the germinal center light and dark zones

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Item Type:Article
Title:PI3 kinase and FOXO1 transcription factor activity differentially control B cells in the germinal center light and dark zones
Creators Name:Sander, S. and Chu, V.T. and Yasuda, T. and Franklin, A. and Graf, R. and Calado, D.P. and Li, S. and Imami, K. and Selbach, M. and Di Virgilio, M. and Bullinger, L. and Rajewsky, K.
Abstract:Phosphatidylinositol 3' OH kinase (PI3K) signaling and FOXO transcription factors play opposing roles at several B cell developmental stages. We show here abundant nuclear FOXO1 expression in the proliferative compartment of the germinal center (GC), its dark zone (DZ), and PI3K activity, downregulating FOXO1, in the light zone (LZ), where cells are selected for further differentiation. In the LZ, however, FOXO1 was expressed in a fraction of cells destined for DZ reentry. Upon FOXO1 ablation or induction of PI3K activity, GCs lost their DZ, owing at least partly to downregulation of the chemokine receptor CXCR4. Although this prevented proper cyclic selection of cells in GCs, somatic hypermutation and proliferation were maintained. Class switch recombination was partly lost due to a failure of switch region targeting by activation-induced deaminase (AID).
Keywords:B-Lymphocytes, Cell Differentiation, Cell Separation, Cytidine Deaminase, Flow Cytometry, Fluorescent Antibody Technique, Forkhead Transcription Factors, Gene Expression Regulation, Germinal Center, Immunoglobulin Class Switching, Immunoglobulin Somatic Hypermutation, Liquid Chromatography, Lymphocyte Activation, Mutant Strains Mice, Phosphatidylinositol 3-Kinases, Polymerase Chain Reaction, Tandem Mass Spectrometry, Animals, Mice
Source:Immunity
ISSN:1074-7613
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:43
Number:6
Page Range:1075-1086
Date:15 December 2015
Additional Information:The complete microarray data are available at the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/projects/geo) under accession number GSE68043.
Official Publication:https://doi.org/10.1016/j.immuni.2015.10.021
PubMed:View item in PubMed

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