Present address: Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA
Bach2 represses plasma cell gene regulatory network in B cells to promote antibody class switch
Article first published online: 15 OCT 2010
Copyright © 2010 European Molecular Biology Organization
The EMBO Journal
Volume 29, Issue 23, pages 4048–4061, December 1, 2010
How to Cite
Muto, A., Ochiai, K., Kimura, Y., Itoh-Nakadai, A., Calame, K. L., Ikebe, D., Tashiro, S. and Igarashi, K. (2010), Bach2 represses plasma cell gene regulatory network in B cells to promote antibody class switch. The EMBO Journal, 29: 4048–4061. doi: 10.1038/emboj.2010.257
There is a Have you seen? (December 2010) associated with this Article.
- Issue published online: 1 DEC 2010
- Article first published online: 15 OCT 2010
- Manuscript Accepted: 21 SEP 2010
- Manuscript Received: 17 FEB 2010
- B cell;
- gene regulatory network
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.