Bence Jones proteins: Powerful tool for fundamental study of protein chemistry and pathophysiology

Bence Jones proteins are typically found in patients with monoclonal plasma cell or related B-cell immunoproliferative disorders. Because of their monoclonal origin and resulting chemical homogeneity much of the fundamental information on immunoglobulin structure came initially from their analysis. Amino acid analyses of these components revealed an N-terminal variable (V) and C-terminal constant (C) domain as well as the existence within the V domain of hypervariable segments that account for the specificity and diversity of antibodies. Over the past three decades, the primary structures of hundreds of light chains (complete and partial), from human and other sources, have been determined, aligned, and archived. Bence Jones proteins and V{sub L} dimers were the crystallizable homogeneous proteins which provided much of the early three-dimensional conformational data that helped explain the structural basis of antibody function. Remarkably, a single Bence Jones protein in two solvent systems (low and high ionic strength) exhibited significant differences in the interactions of the two monomeric subunits comprising the dimer, resulting in substantial variation in the structure of the antigen combining site under the two solution conditions. This observation led to a prediction that heterogeneity of domain interactions may contribute to antibody-antigen interactions. Experimental support for this hypothesis has come from comparisons of the detailed structures of antibody-antigen complexes. The interactions at the interface of the V{sub L} dimer are a function of primary structure and solution conditions. Study of these interactions has led to new information on the relationship between protein structure and function and, as discussed below, can account for specific pathophysiological properties associated with Bence Jones proteins.