Abstract
Dysfunction of receptors for IgG (FcgammaRs) has been thought to be involved in the pathogenesis of systemic lupus erythematosus (SLE). We show that a recently described SLE-associated polymorphism of FcgammaRIIb (FcgammaRIIbT(232)), encoding a single transmembrane amino acid substitution, is functionally impaired. FcgammaRIIbT(232) is unable to inhibit activatory receptors because it is excluded from sphingolipid rafts, resulting in the unopposed proinflammatory signaling thought to promote SLE.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Substitution
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Antigens, CD / genetics*
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Antigens, CD / metabolism*
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B-Lymphocytes / physiology
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Gene Expression Regulation / physiology
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Genotype
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Heterozygote
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Homozygote
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Humans
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Lupus Erythematosus, Systemic / genetics*
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Macrophages / physiology
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Membrane Microdomains / metabolism*
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Polymorphism, Genetic*
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Receptors, IgG / genetics*
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Receptors, IgG / metabolism*
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Signal Transduction / physiology
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U937 Cells
Substances
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Antigens, CD
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Fc gamma receptor IIB
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Receptors, IgG