Abstract
E2A is an essential regulator of early B cell development. Here, we have demonstrated that E2A together with E2-2 controlled germinal center (GC) B cell and plasma cell development. As shown by the identification of regulated E2A,E2-2 target genes in activated B cells, these E-proteins directly activated genes with important functions in GC B cells and plasma cells by inducing and maintaining DNase I hypersensitive sites. Through binding to multiple enhancers in the Igh 3' regulatory region and Aicda locus, E-proteins regulated class switch recombination by inducing both Igh germline transcription and AID expression. By regulating 3' Igk and Igh enhancers and a distal element at the Prdm1 (Blimp1) locus, E-proteins contributed to Igk, Igh, and Prdm1 activation in plasmablasts. Together, these data identified E2A and E2-2 as central regulators of B cell immunity.
© 2016 Wöhner et al.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / immunology*
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / immunology*
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Cytidine Deaminase / genetics
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Cytidine Deaminase / immunology
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Enhancer Elements, Genetic / immunology
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Germinal Center / cytology
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Germinal Center / immunology*
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Immunoglobulin Class Switching / immunology
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Mice
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Mice, Knockout
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Plasma Cells / cytology
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Plasma Cells / immunology*
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Transcription Factor 4
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Basic Helix-Loop-Helix Transcription Factors
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Tcf3 protein, mouse
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Tcf4 protein, mouse
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Transcription Factor 4
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AICDA (activation-induced cytidine deaminase)
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Cytidine Deaminase
Associated data
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RefSeq/NR_046144.1
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GENBANK/BK000964.1