Abstract
It has been suggested that VH4-34 gene segment expression is counter-selected in multiple myeloma (MM) due to a self-tolerance mechanism. We cloned and sequenced a VH4-34 gene segment from bone marrow mononuclear cells of a stage III MM patient. We show that VH4-34 was expressed by the serum IgA myeloma (M)-protein, as demonstrated by reactivity with the VH4-34 specific 9G4 mAb and mass spectrometry (MS). The M-protein had weak reactivity with nuclei. These results demonstrate that VH4-34 may be expressed in secreted IgA M-protein with weak autoreactivity. Thus, counter-selection of VH4-34 is pronounced but not absolute in MM. Mechanisms of how VH4-34 can occasionally be expressed in MM and clinical implications are discussed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Amino Acid Sequence
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Antibodies, Antinuclear / genetics
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Antibodies, Antinuclear / immunology
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Antibodies, Monoclonal / immunology
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Antigen-Antibody Reactions
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Autoimmunity
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B-Lymphocytes / immunology
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B-Lymphocytes / pathology
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Base Sequence
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Clone Cells / immunology
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Clone Cells / pathology
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DNA Mutational Analysis
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Gene Rearrangement, B-Lymphocyte, Heavy Chain
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Gene Rearrangement, B-Lymphocyte, Light Chain
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Genes, Immunoglobulin
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Humans
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Immunoglobulin A / immunology*
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin Variable Region / genetics
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Mass Spectrometry
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Molecular Sequence Data
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Multiple Myeloma / immunology*
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Multiple Myeloma / pathology
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Myeloma Proteins / genetics
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Myeloma Proteins / immunology*
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Neoplastic Stem Cells / immunology
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Neoplastic Stem Cells / pathology
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Polymerase Chain Reaction
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Recombinant Fusion Proteins / immunology
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Self Tolerance
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Sequence Alignment
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Sequence Deletion
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Sequence Homology, Nucleic Acid
Substances
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Antibodies, Antinuclear
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Antibodies, Monoclonal
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Immunoglobulin A
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Immunoglobulin Heavy Chains
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Immunoglobulin Variable Region
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Myeloma Proteins
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Recombinant Fusion Proteins
Associated data
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GENBANK/DQ916278
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GENBANK/DQ916279