Journal article
The transcription factors IRF8 and PU.1 negatively regulate plasma cell differentiation
S Carotta, SN Willis, J Hasbold, M Inouye, SHM Pang, D Emslie, A Light, M Chopin, W Shi, H Wang, HC Morse, DM Tarlinton, LM Corcoran, PD Hodgkin, SL Nutt
Journal of Experimental Medicine | Published : 2014
DOI: 10.1084/jem.20140425
Abstract
Activated B cells undergo immunoglobulin class-switch recombination (CSR) and differentiate into antibody-secreting plasma cells. The distinct transcriptomes of B cells and plasma cells are maintained by the antagonistic influences of two groups of transcription factors: those that maintain the B cell program, including BCL6 and PAX5, and plasma cell-promoting factors, such as IRF4 and BLIMP-1. We show that the complex of IRF8 and PU.1 controls the propensity of B cells to undergo CSR and plasma cell differentiation by concurrently promoting the expression of BCL6 and PAX5 and repressing AID and BLIMP-1. As the PU.1-IRF8 complex functions in a reciprocal manner to IRF4, we propose that conce..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
This work was supported by a National Health and Medical Research Council (NHMRC) of Australia Program grant (575500 and APP1054925 to D. M. Tarlinton, L. M. Corcoran, P. D. Hodgkin, and S. L. Nutt), Victorian State Government Operational Infrastructure Support, Australian Government NHMRC IRIIS, and the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (to H. C. Morse III). S. Carotta was supported by an NHMRC Career Development Award, S. H. M. Pang by the Leukaemia Foundation, M. Inouye and S.N. Willis by NHMRC Post-doctoral Fellowships, S. L. Nutt by an Australian Research Council Future Fellowship, and D. M. Tarlinton, L. M. Corcoran, and P. D. Hodgkin by NHMRC Research Fellowships.