Abstract

BAFF (B cell activating factor belonging to the TNF family) is a cytokine implicated in the survival and maturation of peripheral B lymphocytes and T and B cell activation. BAFF binds to three different receptors: TACI, BCMA and BAFF-R, whose expression is restricted to B and T lymphocytes. BAFF and BAFF-R-deficient mice show a dramatic loss of peripheral B lymphocytes and a severely reduced immune response. In contrast, an enhanced BAFF expression leads to B cell hyperplasia and autoimmunity in mice. In vivo, administration of soluble decoy receptors for BAFF effectively decreases disease progression in various autoimmune mouse models. These evidences render BAFF as a potentially new therapeutic target. Elevated BAFF levels have been detected in the serum of patients with autoimmune diseases, such as Systemic Lupus Erythematosus, rheumatoid arthitis, Sjögren's syndrome, lymphoid cancers and HIV infection. In addition to BAFF receptors, malignant B cells abnormally express BAFF, which attenuates apoptosis through both autocrine and paracrine pathways. The data suggest that an increase in the expression of BAFF induces an enhanced B and T cell activation and the survival of pathologically active B cells. In this article, we review and discuss the participation of BAFF and its receptors in the immune response and its involvement in immunodeficiency, autoimmunity, infections and lymphoid cancers as well as the currently investigated therapies using BAFF antagonists in the treatment of these diseases