title: Gene mutations and alternate RNA splicing result in truncated Ig L chains in human gamma H chain disease.
abstract: The lack of covalently associated L chains features H chain disease proteins produced in some human B cell lymphoproliferative disorders. We cloned and characterized the single rearranged kappa L chain gene from the leukemic lymphocytes of a patient (RIV) affected with gamma 1 H chain disease, to determine the molecular basis for absent L chain. This kappa allele had undergone an effective V-J rearrangement. Extensive somatic mutation focused about the V-J region created a sequence that was only 75% homologous to its germ-line counterpart. Altered acceptor (V kappa) and donor (J kappa) splice sites resulted in an aberrant splice between the leader and C kappa exons and a truncated 850-bp kappa mRNA. RIV leukemic cells as well as myeloma cells transfected with the RIV kappa gene synthesized a truncated protein. Simultaneous defects in H and L chains genes may reflect a hypermutational mechanism for Ig genes in B cells.
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D005803:Genes, Immunoglobulin; D006362:Heavy Chain Disease / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007142:Immunoglobulin gamma-Chains / Q000096:biosynthesis / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis / Q000235:genetics*; D007938:Leukemia / Q000235:genetics / Q000276:immunology; D008214:Lymphocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D021382:Protein Sorting Signals / Q000235:genetics; D012326:RNA Splicing; D012333:RNA, Messenger / Q000302:isolation & purification
chemical_list: D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007142:Immunoglobulin gamma-Chains; D007145:Immunoglobulin kappa-Chains; D021382:Protein Sorting Signals; D012333:RNA, Messenger