Idiotypic characteristics of rheumatoid factors

We have used monoclonal anti-idiotypic antibodies and "sequence-dependent" heterologous anti-peptide antibodies of predefined specificities against either the complementarity determining or framework regions of the human immunoglobulin molecules to delineate the structural and genetic basis of human IgM rheumatoid factor (RF) paraprotein formation. Human IgM RF paraproteins were found to be most commonly reactive with anti-kappa III subgroup anti-sera (88%). These RFs could be subdivided into two major light chain cross reactive idiotype (CRI) groups with the monoclonal antibodies 17.109 and 6B6.6. The two CRI positive light chains are likely encoded by two distinct V kappa germline genes, designated respectively Humkv325 (VkRF) and Humkv328. These CRIs are also associated with specificities other than RFs. Heavy chain analysis of RFs revealed that the product of the Humkv325 gene frequently assemble with heavy chains of the VHI subgroup, but will assemble with the heavy chains of other subgroups less frequently. The VHI heavy chains RFs were found to carry frequently the G6 CRI marker.