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Nature Immunology 9, 927–936 (1 August 2008) | doi:10.1038/ni.1626

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

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.