Silencing and Nuclear Repositioning of the λ5 Gene Locus at the Pre-B Cell Stage Requires Aiolos and OBF-1

Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland.
PLoS ONE (Impact Factor: 3.23). 02/2008; 3(10):e3568. DOI: 10.1371/journal.pone.0003568
Source: PubMed


The chromatin regulator Aiolos and the transcriptional coactivator OBF-1 have been implicated in regulating aspects of B cell maturation and activation. Mice lacking either of these factors have a largely normal early B cell development. However, when both factors are eliminated simultaneously a block is uncovered at the transition between pre-B and immature B cells, indicating that these proteins exert a critical function in developing B lymphocytes. In mice deficient for Aiolos and OBF-1, the numbers of immature B cells are reduced, small pre-BII cells are increased and a significant impairment in immunoglobulin light chain DNA rearrangement is observed. We identified genes whose expression is deregulated in the pre-B cell compartment of these mice. In particular, we found that components of the pre-BCR, such as the surrogate light chain genes lambda5 and VpreB, fail to be efficiently silenced in double-mutant mice. Strikingly, developmentally regulated nuclear repositioning of the lambda5 gene is impaired in pre-B cells lacking OBF-1 and Aiolos. These studies uncover a novel role for OBF-1 and Aiolos in controlling the transcription and nuclear organization of genes involved in pre-BCR function.

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    • "In the bone marrow OBF1 promotes the survival of transitional B cells [14], [15], and is also critical for V(D)J recombination and transcription of a subset of IgVκ genes [21], thereby having an impact on the IgVκ repertoire [22]. In addition, when the OBF1 mutation is combined with a mutation in the zinc finger transcription factor Aiolos, a severe reduction of the immature B cell pool in the bone marrow is observed that defines a crucial function for OBF1 at the preB2 to immature B cell transition [23], [24]. Intriguingly, a recent study has demonstrated that the cytoplasmic p35 isoform of OBF1 interacts with the tyrosine kinase Syk, thus contributing to regulation of preBCR signaling and preB cell proliferation [25]. "
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