TACI Protein

Transmembrane activator and CAML interactor (TACI, TNFRSF13B, CD267) is a TNF receptor superfamily member that serves as one of three receptors for the B-cell cytokines BAFF and APRIL. TACI is expressed on mature B cells, marginal zone B cells and plasma cells (with the ligand-binding ectodomain shed as soluble TACI during inflammation). Ligand engagement triggers TRAF-dependent NF-κB signaling that promotes plasma-cell differentiation, immunoglobulin class switching toward IgA and IgG, and long-lived antibody responses. In vivo, however, TACI exerts an unexpectedly negative regulatory role on B cells: TACI deficiency in humans does not cause immunodeficiency but rather common variable immunodeficiency type 2 with autoimmunity and lymphoproliferation, indicating TACI restrains B-cell expansion. Atacicept (TACI-Ig), a soluble receptor fusion neutralizing both BAFF and APRIL, reduces immunoglobulin production and is in advanced development for multiple sclerosis, IgA nephropathy and lupus. TACI polymorphisms are strongly linked to immunodeficiency and autoimmune risk.