B-cell activating factor receptor (BAFF-R) (BAFF-R)

B-cell activating factor receptor (BAFF-R), also known as TNFRSF13C or CD268, is a critical transmembrane protein belonging to the tumor necrosis factor receptor superfamily [12, 14]. It is primarily expressed on mature B cells and is essential for their survival, maturation, and homeostasis by binding its ligand, BAFF (B-cell activating factor) [1, 2, 11]. Upon ligand binding, BAFF-R activates the non-canonical NF-κB signaling pathway, which prevents B-cell apoptosis and supports the transition from immature to mature B-cell stages [12, 14]. Dysregulation of the BAFF/BAFF-R axis is strongly implicated in the pathogenesis of various autoimmune diseases, such as systemic lupus erythematosus (SLE) and Sjögren's syndrome, where elevated BAFF levels promote the survival of autoreactive B cells [1, 6, 7, 10]. Additionally, BAFF-R is frequently overexpressed in B-cell malignancies, including chronic lymphocytic leukemia (CLL) and various lymphomas, contributing to tumor cell survival [13]. Therapeutic strategies targeting BAFF-R include monoclonal antibodies like ianalumab, which provide a dual mechanism of action by blocking BAFF-mediated survival signals and depleting B cells through antibody-dependent cellular cytotoxicity (ADCC) [1, 4, 5, 6]. Emerging therapies also include BAFF-R-directed CAR T-cell treatments for refractory B-cell hematologic cancers [16].

Other names

Tumor necrosis factor receptor superfamily member 13CCD268B-cell-activating factor receptorBR3BROMARTNFRSF13C

Antagonist of B-cell activating factor (BAFF) binding and induction of antibody-dependent cellular cytotoxicity (ADCC) to deplete B cells.