期刊
NATURE IMMUNOLOGY
卷 9, 期 8, 页码 927-936出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1626
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资金
- Howard Hughes Medical Institute Funding Source: Medline
- NIDDK NIH HHS [R01 DK043726-17, R01 DK43726, R01 DK043726] Funding Source: Medline
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.
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