PREFERENTIAL EXPRESSION OF HUMAN LAMBDA-LIGHT-CHAIN VARIABLE-REGION SUBGROUPS IN MULTIPLE-MYELOMA, AL AMYLOIDOSIS, AND WALDENSTROMS MACROGLOBULINEMIA

We have compared the distribution of lambda-light-chain variable-regio n (V-lambda) subgroups among Ig lambda molecules found in the serum of normal individuals with that of monoclonal Ig lambda components obtai ned from patients with plasma cell and related immunoproliferative dis orders. A panel of monoclonal antibodies specific for each of the majo r human V-lambda subgroups-V-lambda I, V-lambda II, V-lambda III, V-la mbda IV, VlambdaVI, and V-lambda VIII-was used in a highly sensitive e nzyme-linked immunosorbent assay (ELISA) to quantitate each of these p opulations. The mean distribution of Ig lambda I, Ig lambda II, Ig lam bda III, Ig lambda IV, Ig lambda VI, and Ig lambda VIII molecules in s erum specimens collected from 20 normal adults was similar to 40, 3, 4 3, 5, 5, and 3% of the total Ig lambda population, respectively. In co ntrast, that of monoclonal IgG, IgA, and IgD proteins and Bence Jones proteins obtained from patients with multiple myeloma and related gamm opathies (n = 196) was similar to 27, 28, 39, 5, 0, and 1%, respective ly. The percentage of monoclonal Ig lambda II components found in indi viduals with AL lambda amyloidosis (n = 41) was comparably increased t o that seen in multiple myeloma and was even higher in patients with W aldenstrom's macroglobulinemia (n = 16), in whom 63% of the IgM lambda proteins were of the V-lambda II subgroup. Also evidenced were differ ences in the distribution of other V-lambda subgroups in the disease s tates: Most striking was the predominance (41%) of the V-lambda VI sub group among monoclonal lambda chains obtained from patients with AL am yloidosis and that this subgroup was found exclusively on amyloidosis- associated proteins. No Ig lambda VI-type myeloma- or macroglobulinemi a-related proteins were identified. The observed alterations in V lamb da subgroup distribution among ''pathologic'' monoclonal Igs were attr ibuted to the particular disease and not related to the heavy-chain cl ass. Our finding that certain V-lambda subgroups are nonstochastically expressed in lambda-type multiple myeloma, AL amyloidosis, and Walden strom's macroglobulinemia provides evidence for abnormal V-L gene usag e in these disorders and, thus, furnishes new insight into their patho genesis. (C) 1994 Academic Press, Inc.