Cholesterol chelation with methyl-β-cyclodextrin (β-MCD) completely abrogates the protective effect of rHIgM22, suggesting that signaling from lipid rafts is critical for the ability of rHIgM22 to rescue oligodendrocytes from oxidative stress-induced apoptosis. β-MCD rHIgM22 + β-MCD F factor receptors closer to a threshold for full activation induced by substantially less extracellular growth factor.