Abstract
The germinal center (GC) is an anatomic compartment found in peripheral lymphoid organs, wherein B cells undergo clonal expansion, somatic mutation, switch recombination, and reactivate immunoglobulin gene V(D)J recombination. As a result of somatic mutation, some GC B cells develop higher affinity antibodies, whereas others suffer mutations that decrease affinity, and still others may become self-reactive. It has been proposed that secondary V(D)J rearrangements in GCs might rescue B cells whose receptors are damaged by somatic mutations. Here we present evidence that mature human tonsil B cells coexpress conventional light chains and recombination associated genes, and that they extinguish recombination activating gene and terminal deoxynucleotidyl transferase expression when their receptors are cross-linked. Thus, the response of the recombinase to receptor engagement in peripheral B cells is the opposite of the response in developing B cells to the same stimulus. These observations suggest that receptor revision is a mechanism for receptor diversification that is turned off when antigen receptors are cross-linked by the cognate antigen.
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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B-Lymphocytes / metabolism*
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CD40 Antigens / metabolism
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Cells, Cultured
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DNA Nucleotidylexotransferase / biosynthesis
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DNA-Binding Proteins / biosynthesis
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Homeodomain Proteins / biosynthesis
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Humans
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Immunoglobulin Joining Region / genetics*
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Immunoglobulin Light Chains
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Immunoglobulin Light Chains, Surrogate
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Immunoglobulin Variable Region / genetics*
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Immunoglobulin kappa-Chains / immunology
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Immunoglobulin lambda-Chains / immunology
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Membrane Glycoproteins / biosynthesis
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Mice
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Mice, Inbred C57BL
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Nuclear Proteins
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Palatine Tonsil / cytology
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Receptors, Antigen, B-Cell / metabolism*
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Recombination, Genetic*
Substances
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CD40 Antigens
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DNA-Binding Proteins
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Homeodomain Proteins
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Immunoglobulin Joining Region
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Immunoglobulin Light Chains
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Immunoglobulin Light Chains, Surrogate
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Immunoglobulin Variable Region
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Immunoglobulin kappa-Chains
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Immunoglobulin lambda-Chains
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Membrane Glycoproteins
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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
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RAG-1 protein
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DNA Nucleotidylexotransferase