β₂M-specific mAbs exclude growth factor receptors and their substrates from lipid rafts. Shown is the localization of IL-6R gp130, IGF-IRβ, IRS-1, MHC class I, caveolin-1 (Cav-1), and GM1 gangliosides in lipid rafts (fractions 2–5) or nonraft fractions (fractions 7–9) in (A) untreated myeloma cells, (B) IL-6– or IGF-I–activated myeloma cells, (C) IL-6– or IGF-I–activated myeloma cells in the presence of mouse IgG1, and (D) IL-6– or IGF-I–activated myeloma cells in the presence of anti-β₂M mAb D1. The concentrations of IL-6 (10 ng/mL), IGF-I (50 ng/mL), mouse IgG1 (50 μg/mL), and anti-β₂M mAb D1 (50 μg/mL) were used. Lipid rafts were isolated from myeloma cells after treatment. The raft fractions were confirmed by positive staining for GM1 gangliosides and identified by CTB binding and by antibody specific to caveolin-1, a raft-associated protein. Results obtained with D1 mAb on MM.1S myeloma cells from 1 representative experiment of 4 performed are shown. Similar results are obtained with other tumor cell lines, and with anti-β₂M mAb E6.