Abstract
Differentiation of B cells into plasma cells requires X-box binding protein-1 (XBP-1). In the absence of XBP-1, B cells develop normally, but very little immunoglobulin is secreted. XBP-1 controls the expression of a large set of genes whose products participate in expansion of the endoplasmic reticulum (ER) and in protein trafficking. We define a new role for XBP-1 in exerting selective translational control over high and sustained levels of immunoglobulin M (IgM) synthesis. XBP-1(-/-) and XBP-1(+/+) primary B cells synthesize IgM at comparable levels at the onset of stimulation with lipopolysaccharide or CpG. However, later there is a profound depression in synthesis of IgM in XBP-1(-/-) B cells, notwithstanding similar levels of micromRNA. In marked contrast, lack of XBP-1 does not affect synthesis and trafficking of other glycoproteins, or of immunoglobulin light chains. Contrary to expectation, degradation of proteins from the ER, using TCRalpha or US11-mediated degradation of class I major histocompatibility complex molecules as substrates, is normal in XBP-1(-/-) B cells. Furthermore, degradation of membrane mu was unaffected by enforced expression of XBP-1. We conclude that in primary B cells, the XBP-1 pathway promotes synthesis and secretion of IgM, but does not seem to be involved in the degradation of ER proteins, including that of mu chains themselves.
Publication types
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Research Support, N.I.H., Extramural
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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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Animals
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Cell Differentiation / drug effects
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Cell Differentiation / immunology*
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Cell Line
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CpG Islands / immunology
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DNA-Binding Proteins / immunology
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DNA-Binding Proteins / metabolism*
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Endoplasmic Reticulum / immunology
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Endoplasmic Reticulum / metabolism*
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / immunology
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Glycoproteins / immunology
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Glycoproteins / metabolism*
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Histocompatibility Antigens Class I / immunology
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Histocompatibility Antigens Class I / metabolism
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Immunoglobulin Light Chains / biosynthesis
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Immunoglobulin Light Chains / immunology
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Immunoglobulin mu-Chains / biosynthesis*
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Immunoglobulin mu-Chains / genetics
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Immunoglobulin mu-Chains / immunology
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Lipopolysaccharides / pharmacology
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Mice
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Mice, Knockout
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Nuclear Proteins / immunology
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Nuclear Proteins / metabolism*
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Plasma Cells / immunology
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Plasma Cells / metabolism*
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Protein Biosynthesis / drug effects
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Protein Biosynthesis / immunology
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Protein Transport / immunology
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RNA, Messenger / biosynthesis
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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Regulatory Factor X Transcription Factors
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Transcription Factors
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X-Box Binding Protein 1
Substances
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DNA-Binding Proteins
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Glycoproteins
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Histocompatibility Antigens Class I
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Immunoglobulin Light Chains
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Immunoglobulin mu-Chains
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Lipopolysaccharides
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Nuclear Proteins
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RNA, Messenger
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Receptors, Antigen, T-Cell, alpha-beta
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Regulatory Factor X Transcription Factors
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Transcription Factors
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X-Box Binding Protein 1
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Xbp1 protein, mouse