CHARACTERIZATION OF A LIGHT-CHAIN PRODUCT OF THE HUMAN JC-LAMBDA-7 GENE-COMPLEX

The human light chain JC lambda locus is comprised of seven distinct s egments, designated JC lambda 1, JC lambda 2, JC lambda 3, JC lambda 4 , JC lambda 5, JC lambda 6, and JC lambda 7, Whereas three of these se ven represent pseudogenes (Psi C lambda 4, Psi C lambda 5, and Psi C l ambda 6), the JC lambda 1, JC lambda 2, and JC lambda 3 complexes are functional, as demonstrated by the finding of their protein products t hrough sequence analyses of lambda-type Bence Jones proteins and light chains derived from monoclonal Igs. Although the JC lambda 7 segment also appears functional, as evidenced through analysis of lymphocyte-d erived mRNA, heretofore no monoclonal JC lambda 7-containing lambda-ch ains have been identified. Serologically, two distinct isotypic marker s, Meg and Oz, are associated, respectively, with JC lambda 1 and JC l ambda 3 proteins, in contrast to JC lambda 2a components, which do not express these determinants and represent a third isotype. Although an other serologic marker, Ke (Kern), considered a fourth isotype, has be en assigned to the JC lambda 7 complex, this relationship has been que stioned. We now report the primary structural features of a lambda-typ e Bence Jones protein that include the four distinctive residues encod ed by the JC lambda 7 gene segment. This protein, obtained from a pati ent with multiple myeloma and designated MCP, represents the first exa mple of such a molecule and provides definitive evidence that the JC l ambda 7 gene complex is functional, Additionally, comparison of the C lambda sequences of Mcg(-)/Oz(-) Bence Jones proteins MCP and KERN sup ports the contention that the Ke-associated one-residue amino acid var iation at position 152 reflects a C lambda 2 polymorphism and that yet another isotypic marker, provisionally designated Mcp, is encoded by the JC lambda 7 gene segment. Thus, we posit that there are four human JC lambda isotypes, Meg,Ke(-)Oz(-)/Ke(+)Oz(-), Ke(-)Oz(+), and Mcp, t hat represent, respectively, products of the JC lambda 1, JC lambda 2, JC lambda 3, and JC lambda 7 gene complexes.