Somatic mutation and CDR3 lengths of immunoglobulin kappa light chains expressed in patients with rheumatoid arthritis and in normal individuals. Academic Article uri icon

Overview

abstract

  • Immunoglobulin secretion by plasma cells infiltrating synovial membranes is a prominent feature of RA. Previous analyses of a cDNA library generated from synovium of RA patient BC revealed immunoglobulin kappa light chain transcripts with extensive somatic mutation, frequent N region addition, and unexpected variation in the lengths of CDR3 regions which form the center of the antigen binding site. To determine if these characteristics are present in other individuals, we performed reverse transcription-polymerase chain reaction amplification and sequenced > or = 10 V kappa-containing amplicons from nine tissue samples: synovia of three individuals with long-standing RA (including patient BC), PBLs of two of these individuals, and PBLs or splenocytes of four normal individuals. Increased levels of somatic mutation in PBLs appeared to correlate with increased age, which may reflect accumulation of circulating memory cells and/or decreased bone marrow production of naive B lymphocytes. Two of three RA synovial samples and both RA PBL samples exhibited increased proportions of clones with unusual CDR3 lengths. Enrichment for these antibody binding sites could be due to abnormal regulation of the emerging repertoire or to selection for B lymphocytes bearing antibodies of unusual specificity, and may play a role in the pathogenesis of RA.

publication date

  • August 1, 1995

Research

keywords

  • Arthritis, Rheumatoid
  • Binding Sites, Antibody
  • Genes, Immunoglobulin
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains
  • Mutation

Identity

PubMed Central ID

  • PMC185269

Scopus Document Identifier

  • 0029116259

Digital Object Identifier (DOI)

  • 10.1172/JCI118129

PubMed ID

  • 7635977

Additional Document Info

volume

  • 96

issue

  • 2