| First Author | Xu H | Year | 2015 |
| Journal | Nat Immunol | Volume | 16 |
| Issue | 12 | Pages | 1274-81 |
| PubMed ID | 26437243 | Mgi Jnum | J:233874 |
| Mgi Id | MGI:5788242 | Doi | 10.1038/ni.3287 |
| Citation | Xu H, et al. (2015) Regulation of bifurcating B cell trajectories by mutual antagonism between transcription factors IRF4 and IRF8. Nat Immunol 16(12):1274-81 |
| abstractText | Upon recognition of antigen, B cells undertake a bifurcated response in which some cells rapidly differentiate into plasmablasts while others undergo affinity maturation in germinal centers (GCs). Here we identified a double-negative feedback loop between the transcription factors IRF4 and IRF8 that regulated the initial developmental bifurcation of activated B cells as well as the GC response. IRF8 dampened signaling via the B cell antigen receptor (BCR), facilitated antigen-specific interaction with helper T cells, and promoted antibody affinity maturation while antagonizing IRF4-driven differentiation of plasmablasts. Genomic analysis revealed concentration-dependent actions of IRF4 and IRF8 in regulating distinct gene-expression programs. Stochastic modeling suggested that the double-negative feedback was sufficient to initiate bifurcation of the B cell developmental trajectories. |
