Clonal evolution of myeloma cells leads to quantitative changes in immunoglobulin secretion and surface antigen expression.

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Abstract
A cloned population of tumor cells can rapidly produce variants that differ in their quantitative expression of surface proteins and in their rate of immunoglobulin [Ig] secretion. A fresh clonal isolate of [mouse] S107 myeloma cells possessing large amounts of surface IgA was continuously passaged in vitro for 2 yr. During this period, fluorescence-activated cell sorter analysis indicated the development of subpopulations possessing decreased amounts of surface IgA. Cells from these variant subpopulations were isolated by first using the cell sorter to enrich for cells with decreased amounts of surface IgA and then cloning the selected population in soft agar. The 50 sublines that were isolated showed heritable differences in their levels of surface IgA and H-2 antigens and in their rates of myeloma protein secretion. Sublines having large amounts, intermediate amounts or absence of surface IgA also had corresponding large amounts, intermediate amounts or absence of myeloma protein secretion. A decrease or loss of surface Ig did not correlate with a decrease or loss of viral envelope glycoprotein gp71 and H-2 antigens. The variants did not resemble the phenotypes of less-differentiated normal lymphocyte populations of the B[bone marrow-derived]-cell lineage. The isolation and characterization of these variants allowed mechanisms and pathways of tumor cell differentiation to be explored and allowed the regulation and function of cell surface proteins to be studied.