BCMA (The B-cell maturation antigen), also
designated as TNFRSF17, belongs to the tumor necrosis factor receptor
superfamily, which is a family of cytokine receptors. BCMA is encoded by a
2.92-kb TNFRSF17 gene located on the short arm of chromosome 16 (16p13.13) and
composed of 3 exons separated by 2 introns. There are four natural splice
variants of human BCMA that present with different receptor binding affinities,
membrane-anchoring ability, and intracellular domain signaling. BCMA main
ligands are the cytokines B-cell activating factor and a proliferation-inducing
ligand. The interaction between BCMA and its ligands activates the NF-κB
signaling pathway that plays an important role in B-cell proliferation and
maturation and is essential for the survival of long-lived bone marrow plasma
cells. BCMA is expressed preferentially on mature B cells and has minimal
expression on hematopoietic stem cells or other cell types. The BCMA has
emerged as a central target in multiple myeloma (MM). In preclinical studies,
overexpression of BCMA and the interaction with is ligand, a
proliferation-inducing ligand (APRIL), was found to promote MM progression in
vivo and augment MM cell growth and survival through induction of multiple
signaling cascades, including protein kinase B (AKT), MAPK, and nuclear factor
(NF)-κB. Additionally, BCMA has been shown to be solubilized at high levels in
serum of patients with MM (sBCMA). This form of sBCMA binds to B-cell
activating factor (BAFF). The role of BAFF is to stimulate normal B-cell and
plasma cell development; however, this functioning is prevented when it is
bound by BCMA in the serum, thereby leading to decreased polyclonal immunoglobulin
levels in patients with MM.
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