Silencing and Nuclear Repositioning of the λ5 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: San Francisco Public Library of Science 30.10.2008
• Subjects: Biomedical research; Bone marrow; Cell activation; Cell cycle; Chains; Chromatin; Deoxyribonucleic acid; Deregulation; DNA; Fibroblasts; Gene expression; Genes; Genetics and Genomics/Gene Expression; Genetics and Genomics/Gene Function; Immunoglobulins; Immunology; Immunology/Genetics of the Immune System; Immunology/Leukocyte Development; Immunology/Leukocyte Signaling and Gene Expression; Laboratories; Light; Lymphocytes; Lymphocytes B; Medical research; Mice; Proteins; Rodents; Spleen; Transcription; Transcription factors; New York; United States > US; Switzerland
• ISSN: 1932-6203; 1932-6203
• 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 λ5 and VpreB, fail to be efficiently silenced in double-mutant mice. Strikingly, developmentally regulated nuclear repositioning of the λ5 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.