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.

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.