PI3 Kinase and FOXO1 Transcription Factor Activity Differentially Control B Cells in the Germinal Center Light and Dark Zones

Sandrine Sander, Van Trung Chu, Tomoharu Yasuda, Andrew Franklin, Robin Graf, Dinis Pedro Calado, Shuang Li, Koshi Imami, Matthias Selbach, Michela Di Virgilio, Lars Bullinger, Klaus Rajewsky

研究成果: Contribution to journalArticle査読

138 被引用数 (Scopus)

抄録

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).

本文言語英語
ページ(範囲)1075-1086
ページ数12
ジャーナルImmunity
43
6
DOI
出版ステータス出版済み - 2015

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 免疫学
  • 感染症

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