The Role of the BAFF and Lymphotoxin Pathways in B Cell Biology

The tumor necrosis factor (TNF) superfamily plays an important role in the homeostasis and activation of the immune system during development and in the adult. Although the CD40 TNF superfamily member is critical for the intrinsic activation of B cells within germinal centers, other TNF superfamily members such as lymphotoxin and B cell activating factor of tumor necrosis factor (BAFF) are required to shape the environment in which B cells are activated. Specifically, constitutive signaling through the lymphotoxin beta receptor (LTβR) is required to maintain functional aspects of the stromal cells that underpin B cell-rich niches whereas BAFF receptor signaling is critical for the survival of particular B cell subsets. Integration of BAFF- and LTβR-derived signals is key for the generation of an appropriate B cell response to foreign pathogens, and therapeutic targeting of these pathways has the potential to ameliorate disease states in which B cells play a central role.