Use of an anti-idiotypic monoclonal antibody in studying amyloidogenic light chains in cells, urine and fibrils: pathophysiology and clinical implications.
A monoclonal anti-idiotype antibody (IgG1k MoAb 3B11D4) raised against the amyloidogenic DEP lambda chain dimer binds a conformational idiotope also present on the monoclonal DEP IgA immunoglobulin. MoAb 3B11D4 does not recognize the reduced and alkylated lambda chain monomers, nor the 15-17-kDa fibrillar light chain fragments which have the same N-terminal sequence of the urinary light chains. The lack of about 70 amino acid residues of the C terminal of the protein prevents the formation of the self-limiting dimer and may facilitate the deposition of the fragments into amyloid fibrils. MoAb 3B11D4 recognizes the plasma cell clone in bone marrow and 9% of circulating B lymphocytes. Panning experiments demonstrate that this antibody has the capability to selectively eliminate the idiotype positive cells from peripheral blood. Antibodies with these characteristics could become a useful tool for better understanding the pathogenesis of the disease and for new therapeutic options.