Abstract
Lymphocytes usually differentiate into effector cells within days after antigen exposure, except in germinal centers where terminal differentiation is delayed while somatic hypermutation creates high-affinity antibody mutants. Here we investigate whether arrest of terminal differentiation can be mediated by BCL-6, a transcriptional repressor that is expressed by germinal center B cells and is required for this phase of B cell development. We find that BCL-6 suppresses the differentiation of transformed and primary B cells to plasma cells by inhibiting the signal transducer and activator of transcription 3-dependent expression of the major regulator of plasma cell development, the B lymphocyte-induced maturation protein (Blimp-1). This function of BCL-6 as a repressor of B lymphocyte differentiation may also underlie the association between chromosomal translocations of its gene and B cell lymphomas.
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 / cytology*
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B-Lymphocytes / drug effects
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B-Lymphocytes / metabolism
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Cell Differentiation* / drug effects
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Cell Division / drug effects
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Cell Line
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Cell Survival / drug effects
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Cytokines / pharmacology
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DNA-Binding Proteins / antagonists & inhibitors*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Flow Cytometry
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Mice
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Plasma Cells / cytology
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Plasma Cells / drug effects
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Plasma Cells / metabolism
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Positive Regulatory Domain I-Binding Factor 1
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-bcl-6
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Repressor Proteins / metabolism
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STAT3 Transcription Factor
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Trans-Activators / antagonists & inhibitors*
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Trans-Activators / metabolism
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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Cytokines
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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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Repressor Proteins
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STAT3 Transcription Factor
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Stat3 protein, mouse
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Trans-Activators
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Transcription Factors
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Positive Regulatory Domain I-Binding Factor 1