BAFF, APRIL, TWE-PRIL: Whoʹs who?

BAFF and APRIL are two members of the TNF superfamily that have co-stimulatory activity on B cells and contribute to autoimmunity. While BAFF is processed at the cell surface, APRIL is processed inside the cell by a furin-convertase and is able to perform its function only as a soluble factor. However, APRIL can be expressed as a cell surface fusion protein with TWEAK called TWE-PRIL. BAFF can also exist as a soluble molecule and can be detected in human serum. Whether the biological functions controlled by membrane-bound BAFF differ from those triggered by soluble BAFF is unclear. In addition to this complexity, BAFF, an alternative splice isoform of BAFF shows different properties. BAFF can also, in autoimmune disease form heterotrimers with APRIL but the control and function of these heterotrimers remain unclear. In order to understand the function of these molecules we need to elucidate the complexity of the various forms of these members of the TNF family.