BCMA (B cell maturation antigen, CD269, TNFRSF17) is a member of the TNF receptor superfamily. BCMA is expressed in immune organs and mature B lymphocytes. It plays a crucial role in B cell development and autoimmune responses. Activation of BCMA by its ligand promotes B cell differentiation and proliferation. BCMA-induced signaling involves various intracellular activities, including activation of the NF-κB signaling pathway and the MAPK8/JNK pathway.
The ligands of BCMA, B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL), are produced by macrophages and dendritic cells. BAFF and APRIL have soluble trimeric biological activity. BAFF and APRIL also bind to two other receptors, BAFF-R and TACI, which are mainly expressed on B cells.
In multiple myeloma, BCMA is widely expressed at high levels on malignant plasma cells, with increasing expression from normal cells to active multiple myeloma. Therefore, BCMA is a promising tumor target. Additionally, gamma-secretase can cleave surface BCMA to form a soluble form (sBCMA), which not only reduces the density of target antigens but also serves as a soluble decoy to resist immune cells. Hence, combining BCMA-targeting antibodies with gamma-secretase inhibitors represents a new therapeutic approach.
