A VH4-34+ myeloma protein with weak autoreactivity.
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.
Frøyland
Marianne
M
Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway.
Thompson
Keith M
KM
Thorpe
Susan J
SJ
Sahota
Surinder S
SS
Gedde-Dahl
Tobias
T
Bogen
Bjarne
B
D000368:Aged; D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D004252:DNA Mutational Analysis; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology; D009194:Myeloma Proteins / Q000235:genetics / Q000276:immunology*; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000473:pathology; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000276:immunology; D017634:Self Tolerance; D016415:Sequence Alignment; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009194:Myeloma Proteins; D011993:Recombinant Fusion Proteins