title: Variable regions of Ig heavy chain genes encoding antithyrotropin receptor antibodies of patients with Graves' disease.
abstract: We have established EBV-transformed human B cell clones producing monoclonal antithyrotropin receptor antibodies from two patients with Graves' disease. We then isolated and characterized Ig H chain genes of 5 B cell clones with the thyrotropin-binding inhibitor Ig (TBII) activity and 4 B cell clones with the thyroid-stimulating antibody (TSAb) activity. We found that VH gene families used in the 5 TBII clones were all VH-III, although those of the four TSAb clones were diverse, including VH-II, -III, -IV, all -V. Most of VH segments used in TBII and TSAb are commonly used in other autoantibodies and fetal liver repertoire. The frequency of somatic mutations in TBII was higher than that in TSAb. Inasmuch as the same germline VH segment (V3-23) was used for both TBII and TSAb, the frequency and position of somatic mutations may be important for generation of TBII and TSAb.
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
authors.forename: E K
authors.initials: EK
authors.lastname: Shin
authors.forename: T
authors.initials: T
authors.lastname: Akamizu
authors.forename: F
authors.initials: F
authors.lastname: Matsuda
authors.forename: H
authors.initials: H
authors.lastname: Sugawa
authors.forename: J
authors.initials: J
authors.lastname: Fujikura
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.forename: T
authors.initials: T
authors.lastname: Honjo
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation; D011989:Receptors, Thyrotropin / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011989:Receptors, Thyrotropin