Publications & Reports

Formation of Assemblies on Cell Membranes by Secreted Proteins: Molecular Studies of Free Lambda Light Chain Aggregates Found on the Surface of Myeloma Cells.

Hutchinson AT, Malik A, Berkahn MB, Agostino M, To J, Tacchi JL, Djordjevic SP, Turnbull L, Whitchurch CB, Edmundson AB, Jones DR, Raison RL, Ramsland PA


We have described the presence of cell membrane-associated kappa free immunoglobulin light chains (FLC) on the surface of myeloma cells. Notably, the anti-kappaFLC mAb, MDX-1097, is being assessed in clinical trials as a therapy for kappa light chain isotype multiple myeloma. Despite the clinical potential of anti-FLC mAbs, there have been limited studies on characterizing membrane-associated FLCs at a molecular level. Furthermore, it is not known if lambdaFLCs can associate with cell membranes of myeloma cells. In this study, we describe the presence of lambdaFLCs on the surface of myeloma cells. We found that cell surface-associated lambdaFLC are bound directly to the membrane and in an aggregated form. Subsequently, membrane interaction studies revealed that lambdaFLCs interact with saturated zwitterionic lipids such as phosphatidylcholine and phosphatidylethanolamine, and using automated docking, we characterize a potential recognition site for these lipids. Atomic force microscopy confirmed that membrane-associated lambdaFLCs are aggregated. Given our findings, we propose a model whereby individual FLCs show modest affinity for zwitterionic lipids, with aggregation stabilizing the interaction due to multivalency. Notably, this is the first study to image FLCs bound to phospholipids and provides important insights into the possible mechanisms of membrane association by this unique myeloma surface antigen.


  • Journal: The Biochemical Journal
  • Published: 04/07/2013
  • Volume: 454
  • Issue: 3
  • Pagination: 479-89