Abstract
During B lymphocyte development, antibodies are assembled by random gene segment reassortment to produce a vast number of specificities. A potential disadvantage of this process is that some of the antibodies produced are self-reactive. We determined the prevalence of self-reactive antibody formation and its regulation in human B cells. A majority (55 to 75%) of all antibodies expressed by early immature B cells displayed self-reactivity, including polyreactive and anti-nuclear specificities. Most of these autoantibodies were removed from the population at two discrete checkpoints during B cell development. Inefficient checkpoint regulation would lead to substantial increases in circulating autoantibodies.
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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Antibodies, Antinuclear / biosynthesis
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Antibodies, Antinuclear / immunology
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Antibody Diversity
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Antibody Specificity
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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 / physiology
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Cell Differentiation
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Cell Line
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Complementarity Determining Regions / chemistry
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Complementarity Determining Regions / immunology
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Cytosol / immunology
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Genes, Immunoglobulin
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Humans
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Immunoglobulin Heavy Chains / chemistry
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Immunoglobulin Heavy Chains / immunology
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Recombination, Genetic
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Selection, Genetic
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Tumor Cells, Cultured
Substances
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Antibodies, Antinuclear
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Autoantibodies
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Complementarity Determining Regions
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Immunoglobulin Heavy Chains