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
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
FOXtrot and RAGtime in B cellsNature Immunology News and Views (01 Aug 2006)
V(D)J recombinational accessibility?heading in the opposite direction?Nature Immunology News and Views (01 Jun 2004)
See all 6 matches for News And ViewsRESEARCH
Essential role of Id2 in negative regulation of IgE class switchingNature Immunology Article (01 Jan 2003)
Identification of very early lymphoid precursors in bone marrow and their regulation by estrogenNature Immunology Article (01 Aug 2001)
See all 60 matches for Research
