Thursday 27 January 2005
FAS(CD95) is a proapoptotic protein expressed within GCs where it plays an important role in negative selection of B cells.
germline mutations of FAS in autosomal recessive autoimmune lymphoproliferative syndrome type 1A (ALPS1A) (MIM.601859)
somatic mutation of FAS in burn scar-related cutaneous squamous cell carcinoma
somatic mutation of FAS in diffuse large B-cell lymphoma (DLBCL)
- FAS mutations have been reported in up to about 20% of DLBCLs, most commonly within the last exon, which encodes the death domain.
- Such mutations likely act in a dominant-negative manner, destabilizing trimeric FAS receptors.
- Loss of FAS leads to defective affinity maturation and failure to negatively select autoreactive B cells, which may lead to autoimmune disease and persistence of malignant clones.
Mice with FAS and FAS ligand (FAS-L) mutations are prone to development of B-cell lymphomas, as are families with germline FAS mutations and associated autoimmune lymphoproliferative syndrome (ALPS).
Fas-mediated fulminant hepatitis in mice (TNFRSF6)
Wallach D, et al: Tumor necrosis factor receptor and Fas signaling mechanisms. Annu Rev Immunol 17:331, 1999.