The transcription factors IRF8 and PU.1 negatively regulate plasma cell differentiation
Open Access
- 6 October 2014
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 211 (11), 2169-2181
- https://doi.org/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 concentration-dependent competition between these factors controls B cell terminal differentiation.Keywords
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