Abstract
Blimp-1, a transcriptional repressor, drives the terminal differentiation of B cells to plasma cells. Using DNA microarrays, we found that introduction of Blimp-1 into B cells blocked expression of a remarkably large set of genes, while a much smaller number was induced. Blimp-1 initiated this cascade of gene expression changes by directly repressing genes encoding several transcription factors, including Spi-B and Id3, that regulate signaling by the B cell receptor. Blimp-1 also inhibited immunoglobulin class switching by blocking expression of AID, Ku70, Ku86, DNA-PKcs, and STAT6. These findings suggest that Blimp-1 promotes plasmacytic differentiation by extinguishing gene expression important for B cell receptor signaling, germinal center B cell function, and proliferation while allowing expression of important plasma cell genes such as XBP-1.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Binding Sites
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Cell Differentiation
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Cell Line
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DNA-Binding Proteins / physiology
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Gene Expression Profiling
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Gene Expression Regulation
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Humans
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Immunoglobulin Class Switching
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Mice
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Models, Immunological
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Oligonucleotide Array Sequence Analysis
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Plasma Cells / immunology*
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Positive Regulatory Domain I-Binding Factor 1
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-bcl-6
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RNA, Messenger / biosynthesis
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Receptors, Antigen, B-Cell / immunology
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Repressor Proteins / genetics
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Repressor Proteins / physiology*
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Signal Transduction
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Spleen / cytology
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Spleen / immunology
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Transcription Factors / biosynthesis
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Tumor Cells, Cultured
Substances
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DNA-Binding Proteins
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Prdm1 protein, mouse
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-6
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RNA, Messenger
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Receptors, Antigen, B-Cell
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Repressor Proteins
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Transcription Factors
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PRDM1 protein, human
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Positive Regulatory Domain I-Binding Factor 1