Regulation of Immunoglobulin Light-Chain Recombination by the Transcription Factor IRF-4 and the Attenuation of Interleukin-7 Signaling
| Autor: | Tamar Hashimshony, Catherine M. Sawai, Harinder Singh, Kristen Johnson, Jagan M. R. Pongubala, Jane A. Skok, Iannis Aifantis |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Chemokine
Stromal cell Blotting Western Immunology Electrophoretic Mobility Shift Assay Immunoglobulin light chain CXCR4 Mice 03 medical and health sciences Chemokine receptor 0302 clinical medicine Cell Movement Animals Gene Rearrangement B-Lymphocyte Light Chain Immunoprecipitation Immunology and Allergy MOLIMMUNO Enhancer Receptor Transcription factor In Situ Hybridization Fluorescence Oligonucleotide Array Sequence Analysis 030304 developmental biology B-Lymphocytes 0303 health sciences biology Reverse Transcriptase Polymerase Chain Reaction Interleukin-7 Stem Cells Cell Differentiation Flow Cytometry Molecular biology Mice Mutant Strains Infectious Diseases Interferon Regulatory Factors biology.protein Signal Transduction 030215 immunology |
| Zdroj: | Immunity. 28:335-345 |
| ISSN: | 1074-7613 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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