title: The transcription factors IRF8 and PU.1 negatively regulate plasma cell differentiation.
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.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Carotta
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Willis
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Jhagvaral
authors.initials: J
authors.lastname: Hasbold
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Inouye
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Swee Heng Milon
authors.initials: SH
authors.lastname: Pang
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
authors.forename: Dianne
authors.initials: D
authors.lastname: Emslie
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Light
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Chopin
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852.
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Tarlinton
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Corcoran
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Hodgkin
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia Department of Medical Biology, Department of Pathology, Department of Microbiology and Immunology, and Department of Computing and Information Systems, University of Melbourne, Parkville, Victoria 3010, Australia nutt@wehi.edu.au.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D000099185:Interferon Regulatory Factor-8; D000099232:Proto-Oncogene Protein Spi-1; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099185:Interferon Regulatory Factor-8; D000099232:Proto-Oncogene Protein Spi-1; D000099218:Interferon Regulatory Factor-4