CHARACTERIZATION OF THE IMMUNOGLOBULIN LIGHT-CHAIN VARIABLE REGION GENE EXPRESSED IN MULTIPLE-MYELOMA

We studied the organization, diversification and clinical significance of the immunoglobulin light chain (IgL) variable region genes express ed in 17 kappa-chain and 16 lambda-chain producing multiple myeloma (M M) samples. The V genes from 31 MM samples had over 84.9% homology to the known germline V kappa/lambda genes, whereas one V kappa and one V lambda gene had only 75.5% and 65.9% homology, respectively. While al l five J kappa segments were equally used, only J lambda-1 or J lambda -2/3 was used among seven J lambda segments. N nucleotide addition was found at two V kappa-J kappa and five V lambda-J lambda junctions. Th e lambda-chain complementarity determining region (CDR)-3 was longer a nd more variable than the kappa-chain CDR-3 mainly due to junctional f lexibility of V lambda and J lambda segments. Somatic mutations were m ore frequent in the J lambda than the J kappa segments, and were distr ibuted in the CDR-3 as well as the frame work region (FWR)-4. Those of the J kappa segments, however, were limited to FWR-4, In FWR-4, repla cement mutations were clustered at codon 106 of kappa-chain and 103 of lambda-chain. Thus nucleotide mutation or conservation was dependent on position, indicating a structural necessity of IgL for the developm ent of myeloma cells in addition to a non-random distribution of mutat ions. There was no characteristic IgL sequence according to the isotyp e of M-protein, clinical stage or renal complication.