Necroptosis serves as a backup for Caspase-8-mediated apoptosis in B cells and blocks lymphomagenesis

While mitochondrial apoptosis is critical for lymphomagenesis, the role of extrinsic apoptosis, involving Caspase-8, remains elusive. Caspase-8 initiates apoptosis, suppresses necroptosis, and promotes inflammation independent of cell death.

Due to this functional versatility, previous research failed to delineate its role in lymphomagenesis. Here, we demonstrate that B-cell-specific inhibition of Caspase-8 caused an aggressive B-cell malignancy in a subset of mice, resembling human DLBCL. However, most B cells lacking Caspase-8 activity underwent necroptosis, preventing tumor development.