| First Author | Johnson K | Year | 2008 |
| Journal | Immunity | Volume | 28 |
| Issue | 3 | Pages | 335-45 |
| PubMed ID | 18280186 | Mgi Jnum | J:132713 |
| Mgi Id | MGI:3776714 | Doi | 10.1016/j.immuni.2007.12.019 |
| Citation | Johnson K, et al. (2008) Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signaling. Immunity 28(3):335-45 |
| abstractText | Productive rearrangement of the immunoglobulin heavy-chain locus triggers a major developmental checkpoint that promotes limited clonal expansion of pre-B cells, thereby culminating in cell-cycle arrest and rearrangement of light-chain loci. By using Irf4-/-Irf8-/- pre-B cells, we demonstrated that two pathways converge to synergistically drive light-chain rearrangement, but not simply as a consequence of cell-cycle exit. One pathway was directly dependent on transcription factor IRF-4, whose expression was elevated by pre-B cell receptor signaling. IRF-4 targeted the immunoglobulin 3'Ekappa and Elambda enhancers and positioned a kappa allele away from pericentromeric heterochromatin. The other pathway was triggered by attenuation of IL-7 signaling and activated the iEkappa enhancer via binding of the transcription factor E2A. IRF-4 also regulated expression of chemokine receptor Cxcr4 and promoted migration of pre-B cells in response to the chemokine ligand CXCL12. We propose that IRF-4 coordinates the two pathways regulating light-chain recombination by positioning pre-B cells away from IL-7-expressing stromal cells. |
