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

Sebastian Carotta, Simon N Willis, Jhagvaral Hasbold, Michael Inouye, Swee Heng Milon Pang, Dianne Emslie, Amanda Light, Michael Chopin, Wei Shi, Hongsheng Wang, Herbert C Morse III, David M. Tarlinton, Lynn M. Corcoran, Philip D Hodgkin, Stephen L Nutt

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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 concentrationdependent competition between these factors controls B cell terminal differentiation.

Original languageEnglish
Pages (from-to)2169-2181
Number of pages13
Journal Journal of Experimental Medicine
Volume211
Issue number11
DOIs
Publication statusPublished - 6 Oct 2014
Externally publishedYes

Cite this

Carotta, S., Willis, S. N., Hasbold, J., Inouye, M., Pang, S. H. M., Emslie, D., Light, A., Chopin, M., Shi, W., Wang, H., Morse III, H. C., Tarlinton, D. M., Corcoran, L. M., Hodgkin, P. D., & Nutt, S. L. (2014). The transcription factors IRF8 and PU.1 negatively regulate plasma cell differentiation. Journal of Experimental Medicine, 211(11), 2169-2181. https://doi.org/10.1084/jem.20140425