Molecular cloning of anti-SS-A/Ro 60-kDa peptide Fab fragments from infiltrating salivary gland lymphocytes of a patient with Sjögren's syndrome.
Anti-SS-A/Ro antibodies are commonly found in systemic autoimmune diseases such as Sjögren's syndrome and systemic lupus erythematosus, and some of these antibodies appear to be responsible for certain pathological lesions including congenital heart block in neonatal lupus. In this study, we generated three human antibody Fab fragments that specifically bind to SS-A/Ro 60-kd peptide from salivary gland lymphocytes of a patient with Sjögren's syndrome by using a phage-display technique. Sequence analysis demonstrated that two of the three Fab clones (E-42 and E-60) used homologous heavy chains derived from the germline VH gene DP73 in combination with different light chains which were derived from germline V kappa gene L6 and V lambda gene DPL23. The third Fab clone (E-56) used another heavy chain derived from the germline VH gene DP31 in combination with the identical light chain as that of E-42. All three Fab clones revealed a high number of somatic mutations that likely occurred in the context of antigen selection. These findings suggest the restricted usage of VH and VL genes of anti-SS-A/Ro antibodies in salivary gland lymphocytes of the patient.
Suzuki
H
H
Department of Rheumatology, University of Tsukuba, Ibaraki, Japan. suzukihi@md.tsukuba.ac.jp
Takemura
H
H
Suzuki
M
M
Sekine
Y
Y
Kashiwagi
H
H
D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000235:genetics*; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000235:genetics*; D008214:Lymphocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D012469:Salivary Glands / Q000473:pathology*; D012859:Sjogren's Syndrome / Q000276:immunology / Q000473:pathology*
D000974:Antibodies, Antinuclear; D007140:Immunoglobulin Fab Fragments; C035356:SS-A antibodies