Characterization of the immunoglobulin light chain variable region gene expressed in multiple myeloma

Abstract

We studied the organization, diversification and clinical significance of the immunoglobulin light chain (IgL) variable region genes expressed in 17 κ-chain and 16 λ-chain producing multiple myeloma (MM) samples. The V genes from 31 MM samples had over 84.9% homology to the known germline Vκ/λ genes, whereas one Vκ and one Vλ gene had only 75.5% and 65.9% homology, respectively. While all five Jκ segments were equally used, only Jλ-1 or Jλ-2/3 was used among seven Jλ segments. N nucleotide addition was found at two Vκ-Jκ and five Vλ-Jλ junctions. The λ-chain complementarity determining region (CDR)-3 was longer and more variable than the κ-chain CDR-3 mainly due to junctional flexibility of Vλ and Jλ segments. Somatic mutations were more frequent in the Jλ than the Jκ segments, and were distributed in the CDR-3 as well as the frame work region (FWR)-4. Those of the Jκ segments, however, were limited to FWR-4. In FWR-4, replacement mutations were clustered at codon 106 of κ-chain and 103 of λ-chain. Thus nucleotide mutation or conservation was dependent on position, indicating a structural necessity of IgL for the development of myeloma cells in addition to a non-random distribution of mutations. There was no characteristic IgL sequence according to the isotype of M-protein, clinical stage or renal complication.