Abstract
Although null mutations in Igalpha have been identified in patients with defects in B cell development, no mutations in Igbeta have been reported. We recently identified a patient with a homozygous amino acid substitution in Igbeta, a glycine to serine at codon 137, adjacent to the cysteine required for the disulfide bond between Igalpha and Igbeta. This patient has a small percentage of surface IgM(dim) B cells in the peripheral circulation (0.08% compared with 5-20% in healthy controls). Using expression vectors in 293T cells or Jurkat T cells, we show that the mutant Igbeta can form disulfide-linked complexes and bring the mu H chain to the cell surface as part of the BCR but is inefficient at both tasks. The results show that minor changes in the ability of the Igalpha/Igbeta complex to bring the BCR to the cell surface have profound effects on B cell development.
Publication types
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Clinical Trial
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Substitution / immunology
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B-Lymphocytes* / immunology
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CD79 Antigens / genetics*
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CD79 Antigens / immunology
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Cell Differentiation / genetics*
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Cell Differentiation / immunology
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Child, Preschool
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Common Variable Immunodeficiency / genetics*
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Common Variable Immunodeficiency / immunology
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Disulfides / immunology
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Gene Expression
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Genetic Diseases, Inborn / genetics*
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Genetic Diseases, Inborn / immunology
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Homozygote
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Humans
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Immunoglobulin M / genetics
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Immunoglobulin M / immunology
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Immunoglobulin mu-Chains / genetics
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Immunoglobulin mu-Chains / immunology
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Immunoglobulins / genetics
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Immunoglobulins / immunology
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Jurkat Cells
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Mutation, Missense* / immunology
Substances
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CD79 Antigens
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CD79A protein, human
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CD79B protein, human
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Disulfides
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Immunoglobulin M
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Immunoglobulin mu-Chains
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Immunoglobulins
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immunoglobulin B