A patient (Mia) with a monoclonal IgM(kappa) cryoglobulin (cryo IgM) developed additional heavy chain disease proteins of the gamma3 subclass 8 years later. Biochemical studies of the cryo IgM indicated that the heavy chain was VHI, but the NH2-terminal amino acid sequence of the light chain did not permit a definite assignment of its Vkappa subgroup. Two major fragments of the gamma3 chain were distinguishable by electrophoresis in sodium dodecyl sulfate polyacrylamide gel. The smaller component (designated Mia F) had a molecular weight of approximately 30 000 and the larger component (designated Mia S) 35 000. Both fragments had G3m(21) and G3m(27) allotypic determinants. These data and the NH2-terminal amino acid sequence of the gamma chain fragments suggested that Mia S consists of the major part of the gamma3 hinge region plus the CH2 and CH3 domains of the gamma3 chain, whereas Mia F may be derived from the former as a result of postsynthetic cleavage. The partial amino acid sequence of the Mia S fragment is homologous to the hinge region amino acid sequence of human gamma3 chains reported in the literature, with only one amino acid difference out of the 11 residues compared. This difference may represent an allotypic difference within the gamma3 subclass. Alternatively, the production of Mia S may have resulted from the accidental derepression of a "silent" constant region gene not expressed in normal individuals.

Serological and biochemical studies were performed on M components isolated from 3 patients with transitional cell carcinoma of the urinary bladder (TCC). All were IgG1(K) proteins. 2 of the 3 belonged to the V_KI subgroup, and these 2 also possessed cross-reactive idiotypic determinants. These findings are consistent with the ideas that M components in patients with a given kind of cancer may have restricted heterogeneity, and that the synthesis of an M component and the manifestation of a solid tumor may be related events in some patients who exhibit both abnormalities.