title: Blimp-1 controls plasma cell function through the regulation of immunoglobulin secretion and the unfolded protein response.
abstract: Plasma cell differentiation requires silencing of B cell transcription, while it establishes antibody-secretory function and long-term survival. The transcription factors Blimp-1 and IRF4 are essential for the generation of plasma cells; however, their function in mature plasma cells has remained elusive. We found that while IRF4 was essential for the survival of plasma cells, Blimp-1 was dispensable for this. Blimp-1-deficient plasma cells retained their transcriptional identity but lost the ability to secrete antibody. Blimp-1 regulated many components of the unfolded protein response (UPR), including XBP-1 and ATF6. The overlap in the functions of Blimp-1 and XBP-1 was restricted to that response, with Blimp-1 uniquely regulating activity of the kinase mTOR and the size of plasma cells. Thus, Blimp-1 was required for the unique physiological ability of plasma cells that enables the secretion of protective antibody.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Australia.
authors.forename: Julie
authors.initials: J
authors.lastname: Tellier
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Computing and Information Systems, The University of Melbourne, Parkville, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Minnich
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Australia.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liao
authors.affiliation: School of BioSciences, The University of Melbourne, Parkville, Australia.
authors.forename: Simon
authors.initials: S
authors.lastname: Crawford
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Mathematics and Statistics, The University of Melbourne, Parkville, Australia.
authors.forename: Gordon K
authors.identifier: http://orcid.org/0000-0001-9221-2892
authors.initials: GK
authors.lastname: Smyth
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Australia.
authors.forename: Axel
authors.initials: A
authors.lastname: Kallies
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Busslinger
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Australia.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000276:immunology; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D048429:Cell Size; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D007136:Immunoglobulins / Q000276:immunology* / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000071701:Regulatory Factor X Transcription Factors; D017422:Sequence Analysis, DNA; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D056811:Unfolded Protein Response / Q000235:genetics / Q000276:immunology*; D000071717:X-Box Binding Protein 1; D000099218:Interferon Regulatory Factor-4
chemical_list: D051702:Activating Transcription Factor 6; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D050835:Interferon Regulatory Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000071701:Regulatory Factor X Transcription Factors; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; D000099218:Interferon Regulatory Factor-4; C497112:Atf6 protein, mouse; C513258:Prdm1 protein, mouse; C000605544:Xbp1 protein, mouse; C546843:mTOR protein, mouse