Abstract
Receptor editing, clonal deletion, and anergy are the mechanisms by which B cells maintain tolerance to self antigens. To determine the extent to which receptor editing shapes the normal antibody repertoire, we generated an immunoglobulin kappa polymorphism that facilitates the detection of editing of immunoglobulin light chains in vivo. We found that B cells are targeted for editing during a 2-hour delay in development at the pre-BII cell stage, and that about 25% of all antibody molecules are produced by gene replacement. These results suggest that receptor editing represents a major force in shaping the antibody repertoire.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibody Affinity
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Binding Sites, Antibody
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Gene Rearrangement, B-Lymphocyte, Light Chain*
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Genes, Immunoglobulin
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / immunology
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Humans
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Immunoglobulin Constant Regions / genetics
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin kappa-Chains / genetics
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Immunoglobulin kappa-Chains / immunology
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Mice
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Mice, Transgenic
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Models, Immunological
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Nuclear Proteins
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Receptors, Antigen, B-Cell / genetics*
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Receptors, Antigen, B-Cell / immunology*
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Recombination, Genetic
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Self Tolerance*
Substances
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DNA-Binding Proteins
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Immunoglobulin Constant Regions
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Immunoglobulin Heavy Chains
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Immunoglobulin kappa-Chains
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Nuclear Proteins
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RAG2 protein, human
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Rag2 protein, mouse
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Receptors, Antigen, B-Cell
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V(D)J recombination activating protein 2