Free Ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form

• Published in: The Journal of immunology (1950) Vol. 185; no. 7; pp. 4179 - 4188
• Main Authors: Hutchinson, Andrew T, Ramsland, Paul A, Jones, Darren R, Agostino, Mark, Lund, Maria E, Jennings, Cameron V, Bockhorni, Vanessa, Yuriev, Elizabeth, Edmundson, Allen B, Raison, Robert L
• Format: Journal Article
• Language: English
• Published: United States 01.10.2010
• Subjects: Blotting, Western; Cell Line, Tumor; Cell Membrane - chemistry; Cell Membrane - immunology; Cell Membrane - metabolism; Cell Separation; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Immunoglobulin Light Chains - metabolism; Multiple Myeloma - metabolism; Multiple Myeloma - pathology; Multiprotein Complexes; Plasma Cells - metabolism; Plasma Cells - pathology; Receptor Aggregation - physiology; Sphingomyelins - metabolism; Transfection
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1001956

Free κ L chains (FκLCs) are expressed on the surface of myeloma cells and are being assessed as a therapeutic target for the treatment of multiple myeloma. Despite its clinical potential, the mechanism by which FκLCs interact with membranes remains unresolved. In this study, we show that FκLCs associate with sphingomyelin on the plasma membrane of myeloma cells. Moreover, membrane-bound FκLCs are aggregated, suggesting that aggregation is required for intercalation with membranes. Finally, we propose a model where the binding of FκLCs with sphingomyelin on secretory vesicle membranes is stabilized by self-aggregation, with aggregated FκLCs exposed on the plasma membrane after exocytosis. Although it is well known that protein aggregates bind membranes, this is only the second example of an aggregate being found on the surface of cells that also secrete the protein in its native form. We postulate that many other aggregation-prone proteins may associate with cell membranes by similar mechanisms.