| First Author | Muto A | Year | 2010 |
| Journal | EMBO J | Volume | 29 |
| Issue | 23 | Pages | 4048-61 |
| PubMed ID | 20953163 | Mgi Jnum | J:167182 |
| Mgi Id | MGI:4867375 | Doi | 10.1038/emboj.2010.257 |
| Citation | Muto A, et al. (2010) Bach2 represses plasma cell gene regulatory network in B cells to promote antibody class switch. EMBO J 29(23):4048-61 |
| abstractText | Two transcription factors, Pax5 and Blimp-1, form a gene regulatory network (GRN) with a double-negative loop, which defines either B-cell (Pax5 high) or plasma cell (Blimp-1 high) status as a binary switch. However, it is unclear how this B-cell GRN registers class switch DNA recombination (CSR), an event that takes place before the terminal differentiation to plasma cells. In the absence of Bach2 encoding a transcription factor required for CSR, mouse splenic B cells more frequently and rapidly expressed Blimp-1 and differentiated to IgM plasma cells as compared with wild-type cells. Genetic loss of Blimp-1 in Bach2(-/-) B cells was sufficient to restore CSR. These data with mathematical modelling of the GRN indicate that Bach2 achieves a time delay in Blimp-1 induction, which inhibits plasma cell differentiation and promotes CSR (Delay-Driven Diversity model for CSR). Reduction in mature B-cell numbers in Bach2(-/-) mice was not rescued by Blimp-1 ablation, indicating that Bach2 regulates B-cell differentiation and function through Blimp-1-dependent and -independent GRNs. |
