Abstract
The terminal differentiation of B cells into antibody-secreting plasma cells is tightly regulated by a complex network of transcription factors. Here we evaluated the role of the Ets factor Spi-B during terminal differentiation of human B cells. All mature tonsil and peripheral blood B-cell subsets expressed Spi-B, with the exception of plasma cells. Overexpression of Spi-B in CD19(+) B cells inhibited, similar to the known inhibitor BCL-6, the expression of plasma cell-associated surface markers and transcription factors as well as immunoglobulin production, ie, in vitro plasma cell differentiation. The arrest in B-cell differentiation enforced by Spi-B was independent of the transactivation domain, but dependent on the Ets-domain. By chromatin immunoprecipitation and assays using an inducible Spi-B construct BLIMP1 and XBP-1 were identified as direct target genes of Spi-B mediated repression. We propose a novel role for Spi-B in maintenance of germinal center and memory B cells by direct repression of major plasma cell factors and thereby plasma cell differentiation.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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B-Lymphocyte Subsets / cytology
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B-Lymphocyte Subsets / physiology
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Binding Sites / genetics
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Cell Differentiation / physiology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Gene Expression
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Humans
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Immunoglobulins / biosynthesis
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In Vitro Techniques
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Plasma Cells / cytology*
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Plasma Cells / immunology
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Plasma Cells / physiology*
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Positive Regulatory Domain I-Binding Factor 1
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Promoter Regions, Genetic
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-ets / chemistry
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Proto-Oncogene Proteins c-ets / genetics
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Proto-Oncogene Proteins c-ets / physiology*
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Regulatory Factor X Transcription Factors
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Repressor Proteins / genetics
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Repressor Proteins / physiology*
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transduction, Genetic
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X-Box Binding Protein 1
Substances
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DNA-Binding Proteins
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Immunoglobulins
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Proto-Oncogene Proteins c-ets
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Recombinant Proteins
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Regulatory Factor X Transcription Factors
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Repressor Proteins
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Transcription Factors
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X-Box Binding Protein 1
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XBP1 protein, human
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PRDM1 protein, human
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Positive Regulatory Domain I-Binding Factor 1