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

Free ? L chains (F?LCs) 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 F?LCs interact with membranes remains unresolved. In this study, we show that F?LCs associate with sphingomyelin on the plasma membrane of myeloma cells. Moreover, membrane-bound F?LCs are aggregated, suggesting that aggregation is required for intercalation with membranes. Finally, we propose a model where the binding of F?LCs with sphingomyelin on secretory vesicle membranes is stabilized by self-aggregation, with aggregated F?LCs 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. Copyright© 2010 by The American Association of Immunologists, Inc