title: Multifunctional role of the transcription factor Blimp-1 in coordinating plasma cell differentiation.
abstract: The transcription factor Blimp-1 is necessary for the generation of plasma cells. Here we studied its functions in plasmablast differentiation by identifying regulated Blimp-1 target genes. Blimp-1 promoted the migration and adhesion of plasmablasts. It directly repressed genes encoding several transcription factors and Aicda (which encodes the cytidine deaminase AID) and thus silenced B cell-specific gene expression, antigen presentation and class-switch recombination in plasmablasts. It directly activated genes, which led to increased expression of the plasma cell regulator IRF4 and proteins involved in immunoglobulin secretion. Blimp-1 induced the transcription of immunoglobulin genes by controlling the 3' enhancers of the loci encoding the immunoglobulin heavy chain (Igh) and κ-light chain (Igk) and, furthermore, regulated the post-transcriptional expression switch from the membrane-bound form of the immunoglobulin heavy chain to its secreted form by activating Ell2 (which encodes the transcription-elongation factor ELL2). Notably, Blimp-1 recruited chromatin-remodeling and histone-modifying complexes to regulate its target genes. Hence, many essential functions of plasma cells are under the control of Blimp-1.
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Minnich
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tagoh
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Bönelt
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors.forename: Elin
authors.initials: E
authors.lastname: Axelsson
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Fischer
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Cebolla
authors.affiliation: Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, New York, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tarakhovsky
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
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Jaritz
authors.affiliation: Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.
authors.forename: Meinrad
authors.initials: M
authors.lastname: Busslinger
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D054441:Cell Migration Assays, Leukocyte; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology*; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology*; D013058:Mass Spectrometry; D051379:Mice; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D000099218:Interferon Regulatory Factor-4
chemical_list: D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; D050835:Interferon Regulatory Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C513258:Prdm1 protein, mouse