Somatic mutation of the T15 heavy chain gives rise to an antibody with autoantibody specificity.
The S107 IgA kappa-chain myeloma cell line makes an antiphosphocholine antibody of the T15 idiotype. A somatic mutant of this line, U4, makes an immunoglobulin with a single amino acid substitution of an alanine for a glutamic acid at residue 35. This single amino acid change results in a loss of phosphocholine binding activity. However, the U4 immunoglobulin has acquired reactivity with a variety of phosphorylated macromolecules, including double-stranded DNA, protamine, and cardiolipin. Thus, a single amino acid change in the T15 heavy chain can transform an antibacterial antibody into an antibody that resembles the autoantibodies seen in mice and man with autoimmune disease.
D000818:Animals; D000906:Antibodies / Q000032:analysis*; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000235:genetics*; D002460:Cell Line; D006822:Hybrid Cells / Q000276:immunology; D007070:Immunoglobulin A / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007130:Immunoglobulin Idiotypes / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009154:Mutation; D010767:Phosphorylcholine / Q000032:analysis; D010954:Plasmacytoma / Q000276:immunology*; D011863:Radioimmunoassay
D000906:Antibodies; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D010767:Phosphorylcholine