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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Cell Adhesion / genetics
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Cell Adhesion / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Cell Migration Assays, Leukocyte
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Cell Movement / genetics
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Cell Movement / immunology
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Chromatin Immunoprecipitation
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Electrophoretic Mobility Shift Assay
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Enzyme-Linked Immunosorbent Assay
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Flow Cytometry
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Gene Expression Regulation
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HEK293 Cells
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High-Throughput Nucleotide Sequencing
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Humans
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin Heavy Chains / immunology*
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Immunoglobulin kappa-Chains / genetics
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Immunoglobulin kappa-Chains / immunology*
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Interferon Regulatory Factors / genetics
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Interferon Regulatory Factors / immunology*
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Mass Spectrometry
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Mice
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Plasma Cells / immunology*
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Plasma Cells / metabolism
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Positive Regulatory Domain I-Binding Factor 1
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Analysis, DNA
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Sequence Analysis, RNA
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Transcription Factors / genetics
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Transcription Factors / immunology*
Substances
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Immunoglobulin Heavy Chains
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Immunoglobulin kappa-Chains
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Interferon Regulatory Factors
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Prdm1 protein, mouse
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Transcription Factors
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interferon regulatory factor-4
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Positive Regulatory Domain I-Binding Factor 1