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ALPS patients show impaired generation of humoral memory for T independent antigens whereas they generate memory for self-antigens due to impaired FAS-dependent removal of autoreactive germinal center B cells. It is known that FAS signaling via caspase activation results in cell apoptosis. However, FAS ligation may also initiate or modulate non-apoptotic signaling as shown for example by its ability to activate NF-κB. Recent data implicate a regulatory role of FAS in the modulation of mTOR signaling in ALPS double-negative T cells. Moreover, a recently described C194V FAS mutation disturbs its post-translational modification leading to impaired apoptosis induction while non-apoptotic signalling is still intact. Consequently, C194V FAS protects from the autoimmune phenotype in the murine ALPS system. This supports the view that FAS may prevent autoimmunity with other mechanisms than …