Mutations in Mouse Myeloma Cells: Implications for Human Multiple Myeloma and the Production of Immunoglobulins

Abstract

Multiple myeloma raises a number of puzzling questions about the production of immunoglobulins and the malignant transformation of lymphoid cells. Some of these questions can be approached by studying mouse plasmacytomas and by genetic and biochemical studies of mouse myeloma cells in culture. The synthesis, assembly, glycosylation, and secretion of immunoglobulin has been analyzed in detail using the mouse myeloma system. The development of a technique that detects variants in clones of cultured mouse myeloma cells has led to the demonstration of a unique genetic instability in these cells. Based on these results a model is presented to explain the high frequency of light-chain producing (Bence Jones) myelomas in patients. Finally, mutant cell lines have been recovered which produce defective immunoglobulins similar to those found in heavy-chain disease and some other lymphoproliferative disorders.