A highly conserved determinant on human rheumatoid factor idiotypes defined by a mouse monoclonal antibody

Abstract

Different human IgM rheumatoid factor (IgM RF) idiotypes have been described defined by polyclonal rabbit anti-idiotypic antibodies. These antisera do not allow clear genetic analysis of the idiotypic determinants, be they cross-reactive or private. Therefore, we tried to obtain a set of monoclonal anti-idiotypic antibodies directed against RF idiotypes. Purified IgM RF serum from a patient with classical rheumatoid arthritis was used to immunize BALB/c mice. The spleen cells were fused with Sp 2/0 Ag 14, a nonsecreting mouse myeloma cell line, and a hybrid producing monoclonal anti-idiotypic antibody was selected. The mouse antibody, an IgG1 kappa, reacts with an identical or similar determinant located on (or close to) the binding site of all tested monoclonal or polyclonal IgM RF from totally unrelated patients with Waldenströms's macroglobulinemias or rheumatoid arthritis. The monoclonal antibody also reacts with 2 rheumatoid arthritis patients' IgG RF and with a low proportion of normal polyclonal IgM without detectable RF activity. An hypothesis is proposed to explain the existence of a such highly conserved determinant on RF idiotypes.

Idiotypes and the structural diversity of human rheumatoid factors

“…Although the RFs in patients with rheumatoid diseases have been shown to express CRIs [17,19,39,41], the structural or genetic bases for the idiotype expression have not been previously determined. By using the MoAb 17.109, and the heterologous rabbit anti-peptide antisera (anti-PSL2 and anti-PSL3) described above, we have detected the presence of various CRIs on RFs isolated from patients with rheumatoid arthritis or with primary Sjogren's syndrome [55].…”

Complete protein sequences of the variable regions of the cloned heavy and light chains of a human anti-cytomegalovirus antibody reveal a striking similarity to human monoclonal rheumatoid factors of the Wa idiotypic family.

“…The Wa idiotypic family, representing -60% of monoclonal RFs, has been found to be highly restricted in the use of light and heavy chain variable region gene segments (20)(21)(22)(23)(24)(25)(26)(27)(28). This is analogous to the restricted use of immunoglobulin variable region gene segments in murine antigen specific systems, many of which bear cross-reactive idiotypes.…”

Monoclonal antibodies to restricted and cross‐reactive idiotopes on monoclonal rheumatoid factors and their recognition of idiotope‐positive cells

“…The recognition of cross-reactive idiotypes shared by monoclonal and polyclonal R F has been reported by a number of workers [l, 4, 5, 7, 81. Most of these reports have concerned the use of polyclonal anti-idiotypes, although in two cases mAb were used [7, 81; one of these mAb also bound to a proportion of normal IgM in addition to R F [7], but with one exception the mAb against cross-reactive idiotopes which we produced did not show appreciable binding to normal IgM. The Wa idiotype present on about 60% of R F was first reported by Kunkel and colleagues [4]; it is possible that our mAb recognizing a cross-reactive idiotope are detecting this idiotype; proof of this would require comparison with the polyclonal antisera with defined anti-Wa specificity.…”

“…Bona and colleagues raised mAb to a single MRF and used these to demonstrate the existence of homobodies (anti-idiotypes which are "internal images" of the antigen), and "epibodies" (reacting with a cross-reactive structure shared by epitopes and idiotopes on anti-idiotypes against them) [6]. Pasquali and colleagues have also reported a single anti-idiotypic mAb raised against a polyclonal RF, which recognized a highly conserved idiotypic determinant on all RF, although it also bound to a proportion of normal IgM [7]. Carson and Fong reported one mAb reacting with 30% of MRF and suggested this cross-reactive idiotope was related to the complementarity determining region (CDR) of the x light chain [8].…”