A highly conserved conformational idiotope on human IgM rheumatoid factor paraproteins of the Wa cross-reactive idiotype family defined by a monoclonal antibody

Abstract

Human IgM rheumatoid factors have been classified into major (Wa) and minor (Po) idiotypically cross-reactive families on the basis of reactivity with polyclonal anti-idiotypic antisera. Extensive structural studies have revealed that RFs from the Wa CRI family have homologous light chains. The structural basis of this CRI however is not known. In this study we have defined a conformational idiotope requiring the association of the VH and VL of a number of RF from the Wa CRI family for its expression and which thus comprise part of the Wa CRI. A murine monoclonal antibody, G8 specific for the idiotope reacted with 67% of RFs from the Wa CRI family. G8 also reacted with one IgG2K paraprotein with unknown specificity suggesting that the idiotope per se does not confer RF reactivity. Comparative studies of G8 expression relative to previously described sequence-dependent heavy and light chain associated idiotopes suggest that G8 recognises a separate determinant. Furthermore, the G8 idiotope is found on RFs expressing the VHI subgroup of heavy chain. Study of G8 expression in polyclonal IgM in normal sera demonstrated that the idiotope is widely expressed in the population. However, significantly higher levels of IgM bearing G8 were detected in the sera of patients with rheumatoid arthritis.