Abstract
Protein SWAP-70 was initially isolated from nuclei of activated B cells and was implicated in the immunoglobulin class switch process. After B cell activation the protein translocates from the cytoplasm to the nucleus, and may serve to signal nuclear processes. We have generated mice deficient in SWAP-70 and found three main differences when compared to wild-type mice: (i) their B lymphocytes are two- to threefold more sensitive to gamma-irradiation than B cells of wild type; (ii) SWAP-70-deficient mice developed autoantibodies at a much higher frequency; and (iii) the CD40 signaling pathway is compromised in the mutant mice. CD40-dependent switching to the IgE isotype is reduced five- to eightfold in vitro. In SWAP-70-deficient mice, IgE levels prior to immunization were six- to sevenfold lower than in wild-type mice, and after immunization three- to fourfold lower. CD40-induced proliferation was transiently increased in the mutant. LPS-induced switching to other isotypes, however, and LPS-induced proliferation were normal. We propose that SWAP-70 serves a specific role in the CD40 signaling pathway, in particular in the IgE response.
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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Animals
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Apoptosis
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Autoantibodies / biosynthesis
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Autoantibodies / immunology*
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B-Lymphocytes / cytology
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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B-Lymphocytes / radiation effects
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CD40 Antigens / immunology*
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Cell Division
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DNA-Binding Proteins / deficiency*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Gamma Rays
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Gene Targeting
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Guanine Nucleotide Exchange Factors*
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Immunoglobulin Class Switching / genetics
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Immunoglobulin Class Switching / immunology
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Immunoglobulin E / biosynthesis
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Immunoglobulin E / genetics
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Immunoglobulin E / immunology*
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Immunoglobulin G / biosynthesis
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Immunoglobulin G / genetics
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Immunoglobulin G / immunology
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Lipopolysaccharides / immunology
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Lymphocyte Activation
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Mice
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Mice, Knockout
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Minor Histocompatibility Antigens
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Mutation / genetics
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Nuclear Proteins / deficiency*
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Radiation Tolerance
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Signal Transduction
Substances
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Autoantibodies
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CD40 Antigens
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DNA-Binding Proteins
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Guanine Nucleotide Exchange Factors
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Immunoglobulin G
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Lipopolysaccharides
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Minor Histocompatibility Antigens
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Nuclear Proteins
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Swap70 protein, mouse
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Immunoglobulin E