The complexity of the BAFF TNF-family members: Implications for autoimmunity

The B-cell activating factor belonging to the tumor-necrosis factor family BAFF contributes to autoimmune disorders. As such, BAFF might become a therapeutic target. However, this molecule has pleiotropic effects that are as numerous as they are varied. The real effect of each form (spliced, glycosylated, membrane bound, soluble, homotrimerized, heterotrimerized, multimerized) has not been well characterized yet. Consequently, conflicting results, regarding the serum concentrations of BAFF or its functional effect, exist in literature. BAFF quantification based on ELISA commercial kits was indeed found to be inaccurate. The complexity of the various forms of BAFF will be reviewed by focusing on the different structural aspects of the molecule. These data have particular implications for autoimmunity, not only because of the role of these factors on B cell growth and survival, but also their influence on the onset and severity of several autoimmune diseases.

► BAFF offers a cluster of variants and forms. ► BAFF can be membrane bound or soluble, glycosylated or non-glycosylated. ► BAFF can form monomer or trimers (heterotrimers with APRIL or BAFF variants). ► ΔBAFF suppresses BAFF function whereas Δ4BAFF favors BAFF transcription. ► Differences between BAFF forms could modulate the effects of anti-BAFF therapy.