Occurrence of heavy chain of 7S IgM half-molecule whose NH2-terminal sequence is identical with that of κ light chain sequence in patients with Waldenstrom macroglobulinemia

We report a rare case of a half molecule 7S IgM (HM 7SIgM) consisting of a unique μ heavy chain and κ light chain found in blood and urine samples from a patient with primary Waldenstrom macroglobulinemia. A 64kDa abnormal immunoglobulin was detected in serum and urine by immunoblot method, and purified by a two-dimensional SDS-PAGE after separation from IgG and albumin fractions on gel filtration. NH2-terminal amino acid sequence analysis of the heavy chain revealed that residues 1–20 were identical to those of the NH2-terminal region of κ light chain derived from the same patient. This sequence was then followed by a sequence that could not be identified by a computer homology search on the protein database. Using polypeptide segments obtained from the unique μ chain by digestion with endopeptidase, we identified a sequence spanning from residue 127 in the variable region of the known μ chain to residue 19 in the known CH1 domain and a sequence spanning from residues 67–82 in the heavy chain variable region class II. From these results, we concluded that the 64 kDa protein was an abnormal half molecule 7S IgM consisting of a κ light chain and a unique μ heavy chain of 35 kDa polypeptide in which the NH2-terminal 20 amino acids were replaced by 20 amino acids derived from the sequence of κ light chain in the NH2-terminal region.