| First Author | Batista CR | Year | 2017 |
| Journal | J Immunol | Volume | 198 |
| Issue | 4 | Pages | 1565-1574 |
| PubMed ID | 28062693 | Mgi Jnum | J:247785 |
| Mgi Id | MGI:5926569 | Doi | 10.4049/jimmunol.1601709 |
| Citation | Batista CR, et al. (2017) PU.1 Regulates Ig Light Chain Transcription and Rearrangement in Pre-B Cells during B Cell Development. J Immunol 198(4):1565-1574 |
| abstractText | B cell development and Ig rearrangement are governed by cell type- and developmental stage-specific transcription factors. PU.1 and Spi-B are E26-transformation-specific transcription factors that are critical for B cell differentiation. To determine whether PU.1 and Spi-B are required for B cell development in the bone marrow, Spi1 (encoding PU.1) was conditionally deleted in B cells by Cre recombinase under control of the Mb1 gene in Spib (encoding Spi-B)-deficient mice. Combined deletion of Spi1 and Spib resulted in a lack of mature B cells in the spleen and a block in B cell development in the bone marrow at the small pre-B cell stage. To determine target genes of PU.1 that could explain this block, we applied a gain-of-function approach using a PU.1/Spi-B-deficient pro-B cell line in which PU.1 can be induced by doxycycline. PU.1-induced genes were identified by integration of chromatin immunoprecipitation-sequencing and RNA-sequencing data. We found that PU.1 interacted with multiple sites in the Igkappa locus, including Vkappa promoters and regions located downstream of Vkappa second exons. Induction of PU.1 induced Igkappa transcription and rearrangement. Upregulation of Igkappa transcription was impaired in small pre-B cells from PU.1/Spi-B-deficient bone marrow. These studies reveal an important role for PU.1 in the regulation of Igkappa transcription and rearrangement and a requirement for PU.1 and Spi-B in B cell development. |
