Structural Features of Human Light Chains

By Alan Solomon W ITHIN the past decade, studies by molecular geneticists on the composition and organization of immunoglobulin (Ig)-coding genes at the DNA level have vastly increased our understanding of the genetic mechanisms responsible for generating antibody diversity and for linking Ig synthesis to cellular differentiation. This new information, which has far-reaching biological and clinical implications, has come from research on B cell-related lymphocytic and plasma cell tumors and on their monoclonal Ig productsBence Jones proteins, myeloma proteins, and Waldenstr#{246}m macroglobulins. Bence Jones proteins, long recognized as a diagnostic hallmark of multiple myeloma, have a fundamental influence on the pathophysiological manifestations of this disease. Edelman and Gally’st seminal discovery, less than 25 years ago, that Bence Jones proteins represent homogeneous counterparts of Ig light polypeptide chains made evident the importance of these components as materials for the study of the immune system and confirmed their prediction that chemical analyses of Bence Jones proteins would provide a characteristic molecular structure for the light chain. This article updates earlier reviews of the subject23 and summarizes current knowledge of human light chain structure and the molecular genetic events involved in light chain synthesis.