Primary structure of a monoclonal κ chain in myeloma with light chain deposition disease

SUMMARY Previous data suggest that structural abnormalities of immunoglobulin light chains may be responsible for non‐amyloid light chain deposition disease (LCDD). We report on the complete primary sequence deduced from complementary (c)DNA analysis of a normal‐sized κ chain in a case of myeloma‐associated LCDD. The patient's urine contained a κ type Bence‐Jones protein made of monomers and dimers of an unglycosylated κ chain. The bone marrow myeloma cells contained intracellular κ and γ chains by immunofluorescence. Biosynthesis experiments showed the production of normal‐sized γ chains and of κ chains with the same apparent molecular mass (Mr) in SDS gels as the urinary κ chain (26000–27000). These κ chains were secreted as assembled IgG molecules and as a large excess of free monomers and dimers. The complete sequence of two identical cDNA clones derived from a normal‐sized κ messenger RNA indicated that this K chain belonged to the rare V κ IV subgroup. The κ mRNA had an overall normal structure made up of the V κ IV sequence rearranged to J κ IV and followed by a normal constant exon of the Km(3) allotype. The variable region differed from the V κ IV‐J κ I germline sequence by 17 amino acid substitutions. The peculiar sequence of the variable region of this κ chain of a rare subgroup might relate lo its tissue deposition.