Abstract
The transcription factor Blimp-1 induces the maturation of B cells into Ab-secreting plasma cells. DNA microarrays were used to analyze the transcription profiles of both Blimp-1-transduced murine B cell lines and the inducible B cell line BCL(1). Hundreds of genes were differentially regulated, showing how Blimp-1 both restricts affinity maturation and promotes Ab secretion, homeostasis, migration, and differentiation. Strikingly, when different modes of plasma cell induction are used, very different genetic programs are used, suggesting that the transition from a B cell to plasma cell can occur in multiple ways, perhaps accounting for the different types of Ab-secreting cells observed in vivo. Furthermore, mutagenesis of Blimp-1 reveals multiple effector domains, which regulate distinct genes. This indicates that Blimp-1 subdivides the maturation program into select and tunable pathways.
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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3' Untranslated Regions / metabolism
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Amino Acid Motifs / genetics
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Amino Acid Motifs / immunology
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Animals
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B-Lymphocyte Subsets / cytology*
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B-Lymphocyte Subsets / immunology*
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B-Lymphocyte Subsets / 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 Line, Tumor
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Cell Movement / genetics
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Cell Movement / immunology
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Gene Expression Profiling / methods
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Gene Expression Regulation, Neoplastic / immunology*
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Immunoglobulins / biosynthesis
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Lymphocyte Activation / genetics
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Lymphoma / genetics
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Lymphoma / immunology
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Lymphoma / pathology
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Mice
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Mutagenesis, Insertional
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Oligonucleotide Array Sequence Analysis / methods
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Oxidative Stress / genetics
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Oxidative Stress / immunology
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Positive Regulatory Domain I-Binding Factor 1
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Protein Structure, Tertiary / genetics
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RNA Processing, Post-Transcriptional / immunology
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Repressor Proteins / biosynthesis
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Repressor Proteins / chemistry*
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Repressor Proteins / genetics
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Repressor Proteins / physiology*
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Signal Transduction / genetics
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Signal Transduction / immunology
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Transcription Factors / biosynthesis
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Transcription Factors / chemistry*
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transduction, Genetic
Substances
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3' Untranslated Regions
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Immunoglobulins
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Prdm1 protein, mouse
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Repressor Proteins
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Transcription Factors
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Positive Regulatory Domain I-Binding Factor 1