| First Author | Sciammas R | Year | 2011 |
| Journal | Mol Syst Biol | Volume | 7 |
| Pages | 495 | PubMed ID | 21613984 |
| Mgi Jnum | J:203903 | Mgi Id | MGI:5529086 |
| Doi | 10.1038/msb.2011.25 | Citation | Sciammas R, et al. (2011) An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling. Mol Syst Biol 7:495 |
| abstractText | The B-lymphocyte lineage is a leading system for analyzing gene regulatory networks (GRNs) that orchestrate distinct cell fate transitions. Upon antigen recognition, B cells can diversify their immunoglobulin (Ig) repertoire via somatic hypermutation (SHM) and/or class switch DNA recombination (CSR) before differentiating into antibody-secreting plasma cells. We construct a mathematical model for a GRN underlying this developmental dynamic. The intensity of signaling through the Ig receptor is shown to control the bimodal expression of a pivotal transcription factor, IRF-4, which dictates B cell fate outcomes. Computational modeling coupled with experimental analysis supports a model of 'kinetic control', in which B cell developmental trajectories pass through an obligate transient state of variable duration that promotes diversification of the antibody repertoire by SHM/CSR in direct response to antigens. More generally, this network motif could be used to translate a morphogen gradient into developmental inductive events of varying time, thereby enabling the specification of distinct cell fates. |
