c-Myb regulates the T-bet-dependent differentiation program in B cells to coordinate antibody responses
- Author(s)
- Piovesan, D; Tempany, J; Di Pietro, A; Baas, I; Yiannis, C; O'Donnell, K; Chen, Y; Peperzak, V; Belz, GT; Mackay, CR; Smyth, GK; Groom, JR; Tarlinton, DM; Good-Jacobson, KL;
- Details
- Publication Year 2017-04-18,Volume 19,Issue #3,Page 461-470
- Journal Title
- Cell Reports
- Publication Type
- Journal Article
- Abstract
- Humoral immune responses are tailored to the invading pathogen through regulation of key transcription factors and their networks. This is critical to establishing effective antibody-mediated responses, yet it is unknown how B cells integrate pathogen-induced signals to drive or suppress transcriptional programs specialized for each class of pathogen. Here, we detail the key role of the transcription factor c-Myb in regulating the T-bet-mediated anti-viral program. Deletion of c-Myb in mature B cells significantly increased serum IgG2c and CXCR3 expression by upregulating T-bet, normally suppressed during Th2-cell-mediated responses. Enhanced expression of T-bet resulted in aberrant plasma cell differentiation within the germinal center, mediated by CXCR3 expression. These findings identify a dual role for c-Myb in limiting inappropriate effector responses while coordinating plasma cell differentiation with germinal center egress. Identifying such intrinsic regulators of specialized antibody responses can assist in vaccine design and therapeutic intervention in B-cell-mediated immune disorders.
- Publisher
- Cell Press
- Research Division(s)
- Immunology; Bioinformatics; Molecular Immunology
- PubMed ID
- 28423310
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2017.03.060
- Open Access at Publisher's Site
http://www.sciencedirect.com/science/article/pii/S2211124717304217- NHMRC Grants
- NHMRC/1054925, NHMRC/1060675, NHMRC/1058892,
- ARC Grants
- ARC/FT110100283, ARC/FT130100708,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2017-05-02 03:01:29
Last Modified: 2017-05-09 09:45:27