April and Baff Connect Autoimmunity and Cancer

Recent studies of two newcomers to the TNF cytokine family have revealed an unsuspected link between autoimmunity and cancer. In this issue, Rennert et. al. 1 define the specific receptors for the orphan ligand known as APRIL (a proliferation-inducing ligand), which was previously recognized for its growth stimulating activity for tumors of lymphoid, colon, and thyroid origin 2. APRIL binds cell surface receptors B cell maturation antigen (BCMA) and transmembrane activator and CAML interactor (TACI) (see also reference 3); a soluble decoy form of BCMA that antagonizes APRIL's activity inhibits the growth of tumors that naturally overexpress APRIL. What makes this observation biologically intriguing is that the two receptors, BCMA and TACI, were just very recently recognized as receptors for another TNF family member, BAFF, a B lymphocyte activating factor. BAFF is implicated as a key cytokine sustaining...