Muscle-specific tyrosine-protein kinase-reactive B cell receptor (Anti-MuSK BCR)

The Anti-MuSK B cell receptor (BCR) is a membrane-bound immunoglobulin expressed on the surface of B cells that specifically recognizes the muscle-specific tyrosine kinase (MuSK) protein [PubMed: 30634431]. In patients with MuSK-associated myasthenia gravis (MuSK-MG), these B cells differentiate into plasma cells that secrete pathogenic IgG4 autoantibodies [PubMed: 29154140]. These autoantibodies disrupt the neuromuscular junction, leading to severe muscle weakness and respiratory distress. The Anti-MuSK BCR serves as a precise therapeutic target for Chimeric Autoantibody Receptor (CAAR) T cell therapy, such as MuSK-CAART [JCI: 133(14):e167535]. These engineered T cells express the MuSK extracellular domain on their surface, allowing them to selectively identify and eliminate only the B cells that express the MuSK-specific BCR [Science: 353(6295):179-184]. This targeted approach aims to eliminate the source of pathogenic autoantibodies while sparing the rest of the immune system. Unlike traditional immunosuppressants, this strategy potentially offers a durable treatment with fewer systemic side effects [Cabaletta Bio, 2024]. However, the presence of high levels of circulating anti-MuSK antibodies may pose a challenge by potentially neutralizing the CAAR T cells before they reach their cellular targets.

Other names

MuSK-specific B cell receptorAnti-MuSK autoantibody-expressing B cell receptorMuSK-reactive BCRMuscle-specific kinase-reactive B cell receptor

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