Preferential Expression of Human λ-Light-Chain Variable-Region Subgroups in Multiple Myeloma, AL Amyloidosis, and Waldenström's Macroglobulinemia

Abstract

Listen

Translate article

We have compared the distribution of λ-light-chain variable-region ( V λ) subgroups among Igλ molecules found in the serum of normal individuals with that of monoclonal Igλ components obtained from patients with plasma cell and related immunoproliferative disorders. A panel of monoclonal antibodies specific for each of the major human V λ subgroups— V λI, V λII , V λIII, V λIV , V λVI, and V λVIII — was used in a highly sensitive enzyme-linked immunosorbent assay (ELISA) to quantitate each of these populations. The mean distribution of IgλI, IgλII, IgλIII, IgλIV, IgλVI, and IgλVIII molecules in serum specimens collected from 20 normal adults was ∼40, 3, 43, 5, 5, and 3% of the total Igλ population, respectively. In contrast, that of monoclona1 IgG, IgA, and IgD proteins and Bence Jones proteins obtained from patients with multiple myeloma and related gammopathies ( n = 196) was ∼27, 28, 39, 5, 0, and 1%, respectively. The percentage of monoclonal IgλII components found in individuals with ALλ amyloidosis ( n = 41) was comparably increased to that seen in multiple myeloma and was even higher in patients with Waldenström's macroglobulinemia ( n = 16), in whom 63% of the IgMλ proteins were of the V λII subgroup. Also evidenced were differences in the distribution of other V λ subgroups in the disease states: Most striking was the predominance (41%) of the V λVI subgroup among monoclonal λ chains obtained from patients with AL amyloidosis and that this subgroup was found exclusively on amyloidosis-associated proteins. No IgλVI-type myeloma- or macroglobulinemia-related proteins were identified. The observed alterations in Vλ subgroup distribution among "pathologic" monoclonal Igs were attributed to the particular disease and not related to the heavy-chain class. Our finding that certain V λ subgroups are nonstochastically expressed in λ-type multiple myeloma, AL amyloidosis, and Waldenström's macroglobulinemia provides evidence for abnormal V L gene usage in these disorders and, thus, furnishes new insight into their pathogenesis.