Article abstract
Nature Immunology 9, 927 - 936 (2008)
Published online: 22 June 2008 | doi:10.1038/ni.1626
Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros
Damien Reynaud1,2, Ignacio A Demarco2, Karen L Reddy2, Hilde Schjerven3, Eric Bertolino2, Zhengshan Chen2, Stephen T Smale3, Susan Winandy4 & Harinder Singh1,2
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.
- Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois 60637, USA.
- Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, Illinois 60637, USA.
- Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at The University of California at Los Angeles, Los Angeles, California 90095, USA.
- Department of Microbiology-Immunology, Feinberg School of Medicine Northwestern University, Chicago, Illinois 60611, USA.
Correspondence to: Harinder Singh1,2 e-mail: hsingh@uchicago.edu
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