Silencing and nuclear repositioning of the lambda5 gene locus at the pre-B cell stage requires Aiolos and OBF-1

• Published in: PloS one Vol. 3; no. 10; p. e3568
• Main Authors: Karnowski, Alexander, Cao, Chun, Matthias, Gabriele, Carotta, Sebastian, Corcoran, Lynn M, Martensson, Inga-Lill, Skok, Jane A, Matthias, Patrick
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science (PLoS) 2008
• Subjects: Animals; Bone Marrow Cells - metabolism; Bone Marrow Cells - physiology; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Nucleus - genetics; Cells, Cultured; Gene Expression Profiling; Gene Expression Regulation - immunology; Gene Order - physiology; Gene Rearrangement, B-Lymphocyte, Light Chain; Gene Silencing - immunology; Immunoglobulin lambda-Chains - genetics; Immunoglobulin lambda-Chains - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligonucleotide Array Sequence Analysis; Precursor Cells, B-Lymphoid - metabolism; Precursor Cells, B-Lymphoid - physiology; Trans-Activators - genetics; Trans-Activators - physiology
• DOI: 10.1371/journal.pone.0003568

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.