c-Myb regulates the T-bet-dependent differentiation program in B cells to coordinate antibody responses
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
WEHI Research Division(s)
Immunology; Bioinformatics; Molecular Immunology
PubMed ID
28423310
NHMRC Grants
NHMRC/1054925 NHMRC/1060675 NHMRC/1058892
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
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