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.