Role of lipid nanodomains for inhibitory FcγRIIb function.

Our study sheds new light on the molecular mechanisms underlying the regulation of immune signaling mediated by the inhibitory Fcγ receptor (FcγRIIb). By utilizing atomistic simulations and experimental assays, we demonstrate that FcγRIIb interacts with specific lipids in the plasma membrane. Notably, our findings challenge the current view of membrane heterogeneity in immune cells, as FcγRIIb is not localized in specialized membrane domains known as rafts. Rather, we propose that receptor complex formation modulates receptor localization and conformation, thereby enabling ligand binding.Our findings have important implications for understanding how immune receptors function and communicate with each other, and may provide new opportunities for developing therapeutic strategies targeting FcγRIIb in diseases such as autoimmunity and cancer.