Stage-specific control of early B cell development by the transcription factor Ikaros

Tanja A. Schwickert, Hiromi Tagoh, Sinan Gültekin, Aleksandar Dakic, Elin Axelsson, Martina Minnich, Anja Ebert, Barbara Werner, Mareike Roth, Luisa Cimmino, Ross A. Dickins, Johannes Zuber, Markus Jaritz, Meinrad Busslinger

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

The transcription factor Ikaros is an essential regulator of lymphopoiesis. Here we studied its B cell-specific function by conditional inactivation of the gene encoding Ikaros (Ikzf1) in pro-B cells. B cell development was arrested at an aberrant 'pro-B cell' stage characterized by increased cell adhesion and loss of signaling via the pre-B cell signaling complex (pre-BCR). Ikaros activated genes encoding signal transducers of the pre-BCR and repressed genes involved in the downregulation of pre-BCR signaling and upregulation of the integrin signaling pathway. Unexpectedly, derepression of expression of the transcription factor Aiolos did not compensate for the loss of Ikaros in pro-B cells. Ikaros induced or suppressed active chromatin at regulatory elements of activated or repressed target genes. Notably, binding of Ikaros and expression of its target genes were dynamically regulated at distinct stages of early B lymphopoiesis.

Original languageEnglish (US)
Pages (from-to)283-293
Number of pages11
JournalNature Immunology
Volume15
Issue number3
DOIs
StatePublished - Mar 2014
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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