Structural similarities in the kappa light chains of human rheumatoid factor paraproteins and serum immunoglobulins bearing a cross-reactive idiotype.
The monoclonal antibody (MoAb) 17.109 recognizes a cross-reactive idiotype (CRI) associated with the light chains of Waldenstrom's macroglobulins with rheumatoid factor (RF) activity. The MoAb also reacts with a proportion of IgM-RF molecules from the sera of rheumatoid arthritis and primary Sjogren's syndrome patients, and from the sera of seropositive normal human subjects. In the present experiments, we used affinity chromatography to purify the 17.109 CRI-positive immunoglobulin from serum and have analyzed the isolated material by Western blotting. The purified 17.109 CRI-positive material from the sera of rheumatoid arthritis patients, Sjogren's syndrome patients, and normal subjects contained exclusively kappa light chains, and had demonstrated RF activity. In every case the 17.109 CRI-positive isolates reacted with antibodies against synthetic peptides corresponding to both the conserved second and third complementarity-determining regions (CDR) of the monoclonal kappa IgM-RF paraprotein Sie. The binding was inhibited specifically by the free peptides in solution. The antipeptide antibodies did not react appreciably with unfractionated human immunoglobulin. The data establish that the 17.109 CRI-positive immunoglobulin from diverse human sera have similar or identical second and third light chain CDR. These results suggest i) that the MoAb 17.109 identifies the protein product of a single or a very few V kappa genes, ii) that the ability to make kappa light chains with the 17.109-associated variable region is widespread in the human population, and iii) that the 17.109-defined kappa variable region segment is associated with IgM-RF autoantibodies.
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D003429:Cross Reactions; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology*; D009842:Oligopeptides / Q000276:immunology; D010266:Paraproteins / Q000235:genetics / Q000276:immunology*; D012217:Rheumatoid Factor / Q000235:genetics / Q000276:immunology*
D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D009842:Oligopeptides; D010266:Paraproteins; D012217:Rheumatoid Factor