| First Author | Roy K | Year | 2019 |
| Journal | Immunity | Volume | 50 |
| Issue | 3 | Pages | 616-628.e6 |
| PubMed ID | 30850343 | Mgi Jnum | J:282320 |
| Mgi Id | MGI:6380937 | Doi | 10.1016/j.immuni.2019.02.004 |
| Citation | Roy K, et al. (2019) A Regulatory Circuit Controlling the Dynamics of NFkappaB cRel Transitions B Cells from Proliferation to Plasma Cell Differentiation. Immunity 50(3):616-628.e6 |
| abstractText | Humoral immunity depends on efficient activation of B cells and their subsequent differentiation into antibody-secreting cells (ASCs). The transcription factor NFkappaB cRel is critical for B cell proliferation, but incorporating its known regulatory interactions into a mathematical model of the ASC differentiation circuit prevented ASC generation in simulations. Indeed, experimental ectopic cRel expression blocked ASC differentiation by inhibiting the transcription factor Blimp1, and in wild-type (WT) cells cRel was dynamically repressed during ASC differentiation by Blimp1 binding the Rel locus. Including this bi-stable circuit of mutual cRel-Blimp1 antagonism into a multi-scale model revealed that dynamic repression of cRel controls the switch from B cell proliferation to ASC generation phases and hence the respective cell population dynamics. Our studies provide a mechanistic explanation of how dysregulation of this bi-stable circuit might result in pathologic B cell population phenotypes and thus offer new avenues for diagnostic stratification and treatment. |
