APRIL Proteins

APRIL Protein is a cytokine and an independent secretory ligand belongs to TNF family. It binds to TNFRSF13B/TACI and to TNFRSF17/BCMA. APRIL Protein plays a role in the regulation of tumor cell growth, may involve in monocyte/macrophage-mediated immunological processes^[1]. APRIL Protein is produced by myeloid cells and their precursors in the bone marrow. APRIL Protein is retained by surrounding tissues and via HSPG (heparan sulfate proteoglycans) is not retained. It accumulates in large amounts in the bone marrow, leading to more rapid cell maturation and peripheral burst. As for infection response, tonsil mucosa neutrophils present within the infected tissue were the main source of APRIL Protein, whereas keratinocytes were the primary source of APRIL Protein in tissues showing no symptoms of infection^[2]. APRIL Protein acts function by binding BCMA (B cell maturation antigen) and TACI (transmembrane activator and CAML-interactor) and competes with TALL-I (also called BLyS or BAFF) for receptor binding. Soluble BCMA and TACI specifically prevent binding of APRIL Protein and block APRIL-stimulated proliferation of primary B cells, and soluble BCMA is a dominant-negative molecule capable of inhibiting antibody production in vivo. Thus, APRIL Protein stimulates in vitro the proliferation of primary lymphocytes, in addition to lymphoma cell lines, and promotes in vivo the accumulation of B cells in the spleen. Therefore, APRIL-TALL-I and BCMA-TACI form a two ligands-two receptors pathway involved in stimulation of B and T cell function. Moreover, APRIL Protein is also a stimulator of tumor cell growth although TNRF death ligand-1 (TRDL-1), which induces tumor cell apoptosis^[1]. It is a type II membrane protein with a cytoplasmic domain, a hydrophobic transmembrane region, and an extracellular domain^[2]. Mouse and human APRIL proteins are 82% identical in the COOH-terminal part of the extracellular domain, which contains the presumed receptor-binding domain. And the protein sequences of human and mouse are different with similarity of 80.91%^[1]. Nowadays, the APRIL protein is most often studied in the context of lymphoid malignancies.