Beta-2-glycoprotein I-specific B cell receptor (B2GPI-specific BCR)

The beta-2-glycoprotein I-specific B cell receptor (B2GPI-specific BCR) is a membrane-bound immunoglobulin complex expressed on the surface of B lymphocytes that specifically recognizes the protein beta-2-glycoprotein I (B2GPI), also known as apolipoprotein H (Source: UniProt, P02749). In the context of antiphospholipid syndrome (APS), B cells expressing this specific receptor escape immune tolerance and differentiate into plasma cells that secrete pathogenic anti-B2GPI autoantibodies (Source: PubMed, PMID: 31555048). These autoantibodies are the primary drivers of the clinical manifestations of APS, including venous and arterial thrombosis and pregnancy-related complications, by inducing a pro-inflammatory and pro-coagulant state in endothelial cells and platelets (Source: StatPearls, NBK531487). As a therapeutic target, the B2GPI-specific BCR is unique because it allows for the highly selective depletion of the autoreactive B cell population responsible for the disease while leaving the rest of the immune system intact. Experimental therapies, such as Chimeric Autoantibody Receptor (CAAR) T cells, are being engineered to express the B2GPI antigen on their surface to act as a bait, specifically binding to and eliminating B cells that carry the B2GPI-specific BCR (Source: Cabaletta Bio). This precision approach aims to provide a curative treatment for APS with fewer side effects than broad immunosuppressive agents.

Other names

Anti-beta-2-glycoprotein I B cell receptorApolipoprotein H-specific B cell receptorB2GPI-reactive B cell receptor

Selective depletion of B2GPI-specific B cells via Chimeric Autoantibody Receptor (CAAR) T-cell mediated cytotoxicity.