Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros

Damien Reynaud, Ignacio A. Demarco, Karen L. Reddy, Hilde Schjerven, Eric Bertolino, Zhengshan Chen, Stephen T. Smale, Susan Winandy, Harinder Singh

Research output: Contribution to journalArticlepeer-review

Abstract

The transcription factor Ikaros is essential for B cell development. However, its molecular functions in B cell fate specification and commitment have remained elusive. We show here that the transcription factor EBF restored the generation of CD19+ pro-B cells from Ikaros-deficient hematopoietic progenitors. Notably, these pro-B cells, despite having normal expression of the transcription factors EBF and Pax5, were not committed to the B cell fate. They also failed to recombine variable gene segments at the immunoglobulin heavy-chain locus. Ikaros promoted heavy-chain gene rearrangements by inducing expression of the recombination-activating genes as well as by controlling accessibility of the variable gene segments and compaction of the immunoglobulin heavy-chain locus. Thus, Ikaros is an obligate component of a network that regulates B cell fate commitment and immunoglobulin heavy-chain gene recombination.

Original languageEnglish (US)
Pages (from-to)927-936
Number of pages10
JournalNature Immunology
Volume9
Issue number8
DOIs
StatePublished - Aug 2008
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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