Molecular characterization of a nonsecreting myeloma mutant.
The nonsecreting myeloma mutant, NSII/1, derived from MOPC 21 a mouse myeloma cell line, does not produce L chains and expresses a smaller than normal gamma 1 heavy chain, H* (Cowan, Secher and Milstein, J. Mol. Biol. 1974. 90: 691). The free H* is not secreted, but secretion can be rescued in hybrids expressing a light chain. By sequencing L and H chain-cloned cDNA derived from NSII/1 we find only one light chain mRNA expressed which belongs to an aberrantly rearranged kappa gene. We also find that the H* heavy chain is the result of a point mutation. H* mRNA contains an A instead of the G found in wild type at position 1125. The corresponding tryptophan 406 becomes a chain termination, giving rise to a 67 amino acid deletion at the C-terminus. The H* is core-glycosylated, but its state of assembly is abnormal: H* forms high molecular weight, S-S-bonded complexes. The results are discussed with reference to the putative toxic properties of free heavy chains and the failure of some chains to be secreted.
D000818:Animals; D004270:DNA, Circular / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000235:genetics; D007147:Immunoglobulin Light Chains; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010954:Plasmacytoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger; D014158:Transcription, Genetic
D004270:DNA, Circular; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D012333:RNA, Messenger