Monoclonal autoantibodies from patients with autoimmune diseases: synovial fluid B lymphocytes of a patient with rheumatoid arthritis produced an IgG lambda antibody recognizing J-sequences of Ig kappa chains in a conformation-dependent way

Immunobiology. 1999 Jun;200(2):205-14. doi: 10.1016/s0171-2985(99)80070-9.

Abstract

Synovial fluid B cells from a patient with seronegative rheumatoid arthritis were immortalized by electrofusion. The specificity of clone FKN-E12 (IgG1 lambda) was analysed by screening a phage display random peptide library. One heptamer sequence was identified (RASFp1 = HLTFGPG). Three human IgG kappa antibodies contained a highly homologous sequence (xLTFGPG) at the junction of V- and J-regions. Homologies were also found in distinct humans (J kappa 3, J kappa 4) and murine (J kappa 5) J kappa-sequences (TFGPG, LTFGxG), and to a lower degree in all remaining J kappa-sequences (TFGxG). Binding and binding inhibition assays showed that FKN-E12 bound to kappa light chains tested in a conformation-dependent way: it reacted only with IgG kappa or IgA kappa chains adhered to a plastic surface, but not in soluble form. In conclusion, FKN-E12 detects a conformational epitope on probably all kappa light chains, which could be definded by screening a phage library displaying linear epitopes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology*
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies / immunology*
  • B-Lymphocytes / immunology*
  • Humans
  • Hybridomas
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin Joining Region / genetics
  • Immunoglobulin Joining Region / immunology*
  • Immunoglobulin kappa-Chains / genetics
  • Immunoglobulin kappa-Chains / immunology*
  • Immunoglobulin lambda-Chains / biosynthesis*
  • Immunoglobulin lambda-Chains / genetics
  • Male
  • Mice
  • Middle Aged
  • Molecular Sequence Data
  • Peptide Library
  • Protein Conformation
  • Synovial Fluid / cytology

Substances

  • Antibodies, Monoclonal
  • Autoantibodies
  • Immunoglobulin G
  • Immunoglobulin Joining Region
  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains
  • Peptide Library