title: 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 kappa-chain and 16 lambda-chain producing multiple myeloma (MM) samples. The V genes from 31 MM samples had over 84.9% homology to the known germline Vkappa/lambda genes, whereas one Vkappa and one Vlambda gene had only 75.5% and 65.9% homology, respectively. While all five Jkappa segments were equally used, only Jlambda-1 or Jlambda-2/3 was used among seven Jlambda segments. N nucleotide addition was found at two Vkappa-Jkappa and five Vlambda-Jlambda junctions. The lambda-chain complementarity determining region (CDR)-3 was longer and more variable than the kappa-chain CDR-3 mainly due to junctional flexibility of Vlambda and Jlambda segments. Somatic mutations were more frequent in the Jlambda than the Jkappa segments, and were distributed in the CDR-3 as well as the frame work region (FWR)-4. Those of the Jkappa segments, however, were limited to FWR-4. In FWR-4, replacement 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 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.
authors.affiliation: Department of Infectious Diseases, Nagoya University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kiyoi
authors.forename: K
authors.initials: K
authors.lastname: Naito
authors.forename: R
authors.initials: R
authors.lastname: Ohno
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: T
authors.initials: T
authors.lastname: Naoe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D001483:Base Sequence; D005260:Female; D015870:Gene Expression; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin / Q000235:genetics; D006801:Humans; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D007133:Immunoglobulin Joining Region; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains