title: A systematic approach to defining the germline gene counterparts of a mutated autoantibody from a patient with rheumatoid arthritis.
abstract: OBJECTIVE
  To define the germline counterparts of potentially highly mutated autoantibodies in disease states.
  
  
  METHODS
  We developed a systematic approach by first characterizing a rearranged Ig gene and its upstream flank, and then designing suitable primers to amplify specifically the putative germline counterpart.
  
  
  RESULTS
  We identified and characterized the germline counterpart of a rheumatoid factor heavy chain variable region.
  
  
  CONCLUSIONS
  We showed unequivocally that the heavy chain of a rheumatoid factor, derived from synovial tissue, has 4 replacement mutations from the corresponding germline gene. The technique allows quick assessment of the degree of somatic mutation in many autoantibodies, and thus can help to elucidate the underlying mechanisms for the induction and sustained production of such antibodies in patients.
authors.affiliation: Department of Medicine, University of California, San Diego 92093.
authors.forename: R W
authors.initials: RW
authors.lastname: Soto-Gil
authors.forename: T
authors.initials: T
authors.lastname: Olee
authors.forename: B K
authors.initials: BK
authors.lastname: Klink
authors.forename: T P
authors.initials: TP
authors.lastname: Kenny
authors.forename: D L
authors.initials: DL
authors.lastname: Robbins
authors.forename: D A
authors.initials: DA
authors.lastname: Carson
authors.forename: P P
authors.initials: PP
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000235:genetics*; D001483:Base Sequence; D015342:DNA Probes; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012217:Rheumatoid Factor / Q000235:genetics
chemical_list: D001323:Autoantibodies; D015342:DNA Probes; D007143:Immunoglobulin Heavy Chains; D012217:Rheumatoid Factor