Abstract
The generation of high-affinity antibodies requires germinal center (GC) development and differentiation of long-lived plasma cells in a multilayered process that is tightly controlled by the activity of multiple transcription factors. Here, we reveal a new layer of complexity by demonstrating that dynamic changes in Id3 and E-protein activity govern both GC and plasma cell differentiation. We show that down-regulation of Id3 in B cells is essential for releasing E2A and E2-2, which in a redundant manner are required for antigen-induced B cell differentiation. We demonstrate that this pathway controls the expression of multiple key factors, including Blimp1, Xbp1, and CXCR4, and is therefore critical for establishing the transcriptional network that controls GC B cell and plasma cell differentiation.
© 2016 Gloury 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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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Germinal Center / immunology*
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Inhibitor of Differentiation Proteins / genetics
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Inhibitor of Differentiation Proteins / immunology*
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Mice
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Mice, Knockout
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Plasma Cells / immunology*
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Positive Regulatory Domain I-Binding Factor 1
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Receptors, CXCR4 / genetics
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Receptors, CXCR4 / immunology
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Transcription Factor 4
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Transcription Factors / genetics
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Transcription Factors / immunology
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X-Box Binding Protein 1 / genetics
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X-Box Binding Protein 1 / immunology
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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CXCR4 protein, mouse
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Inhibitor of Differentiation Proteins
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Prdm1 protein, mouse
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Receptors, CXCR4
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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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Transcription Factors
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X-Box Binding Protein 1
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Xbp1 protein, mouse
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Idb3 protein, mouse
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Positive Regulatory Domain I-Binding Factor 1