title: A natural autoantibody is encoded by germline heavy and lambda light chain variable region genes without somatic mutation.
abstract: While nonmutated germline variable region (V) genes have been found to encode heavy or light chains of various human autoantibodies, the use of germline V genes by both chains of a given autoantibody has not been documented. Recently, we reported that the heavy chain V gene (designated Humha346) of the Kim4.6 anti-DNA antibody is identical to a germline VH gene, 1.9III. To investigate whether this autoantibody was entirely germline encoded, we searched for the germline counterpart to the Kim4.6 V lambda segment (designated Humla146) and isolated a V lambda I gene designated Humlv117, which was identical to Humla146. Together with the sequence identity of the Kim4.6/Humha346 and 1.9III VH genes, the current data provide the first direct proof that an autoantibody can be encoded entirely by germline V genes without any somatic change. In addition, Humlv117 is the first V lambda I germline gene that has been isolated, and is highly homologous to the V lambda genes expressed in two lymphomas. Thus, this V lambda I gene should provide a useful tool for investigating the expression of the human V lambda gene repertoire, particularly with regard to autoimmune and/or lymphoproliferative diseases.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: K A
authors.initials: KA
authors.lastname: Siminovitch
authors.forename: V
authors.initials: V
authors.lastname: Misener
authors.forename: P C
authors.initials: PC
authors.lastname: Kwong
authors.forename: Q L
authors.initials: QL
authors.lastname: Song
authors.forename: P P
authors.initials: PP
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000235:genetics*; D001324:Autoantigens / Q000276:immunology; D001483:Base Sequence; D004247:DNA / Q000276:immunology*; D005803:Genes, Immunoglobulin / Q000235:genetics*; D005854:Germ Cells; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D012689:Sequence Homology, Nucleic Acid
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains; D004247:DNA