The transcription factors IRF8 and PU.1 negatively regulate plasma cell differentiation

2014/10/06 by Sebastian Carotta, Simon N. Willis, Jhagvaral Hasbold +13 · 25 citations
Immunology and Microbiology · Medicine · #T-cell and B-cell Immunology #Immune Cell Function and Interaction #Cytomegalovirus and herpesvirus research

paper · pdf · 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 concentration-dependent competition between these factors controls B cell terminal differentiation.

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