Journal article
c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses
D Piovesan, J Tempany, A Di Pietro, I Baas, C Yiannis, K O'Donnell, Y Chen, V Peperzak, GT Belz, CR Mackay, GK Smyth, JR Groom, DM Tarlinton, KL Good-Jacobson
Cell Reports | Published : 2017
Open access
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 c..
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Awarded by Multiple Myeloma Research Foundation
Funding Acknowledgements
We thank Colby Zaph, Brendan Russ, and Stephen Turner for critical reading of this manuscript; members of the Good-Jacobson, Tarlinton, and Groom labs for technical assistance; Adele Barugahare and David Powell from the Monash Bioinformatics Platform for additional bioinformatic assistance; and Remy Robert for assistance with the hCXCR3 mice. We also thank Susan Kaech for providing Tbx21<SUP>f/f</SUP> mice. This work was supported by a National Health and Medical Research Council (NHMRC) project grant to K. L. G.-J. (1057707), an NHMRC program grant to D.M.T. and G.T.B. (1054925), and a Leukaemia Foundation grant-in-aid to K. L. G.-J. K. L. G.-J. is supported by an NHMRC Career Development Fellowship (1108066), and D.M.T. and G.K.S. are supported by NHMRC Research Fellowships (1060675 and 1058892, respectively). V.P. was supported by fellowships from the Multiple Myeloma Research Foundation and the European Molecular Biology Organization (ALTF 1337-2010). G.T.B. and J.R.G. are supported by Australian Research Council Future Fellowships (FT110100283 and FT130100708, respectively). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.