Anti-muscle-specific kinase B cell receptor (Anti-MuSK BCR) (Anti-MuSK BCR)

The Anti-muscle-specific kinase B cell receptor (Anti-MuSK BCR) is a specialized surface immunoglobulin expressed on the membrane of autoreactive B cells in patients suffering from MuSK-positive Myasthenia Gravis (MuSK-MG) (StatPearls, 2023). This receptor is responsible for the specific recognition of Muscle-Specific Kinase (MuSK), a transmembrane tyrosine kinase that is vital for the clustering of acetylcholine receptors and the maintenance of the neuromuscular junction (PubMed, PMID: 31138703). In the context of disease, B cells harboring this BCR differentiate into plasma cells that secrete pathogenic IgG4 autoantibodies; these antibodies block the interaction between MuSK and its co-receptor LRP4, leading to impaired synaptic transmission and progressive muscle weakness (Nature Communications, 2020). The Anti-MuSK BCR serves as a high-precision therapeutic target for Chimeric Autoantibody Receptor T (CAART) cell therapy, such as MuSK-CAART (Science, 2016). These engineered T cells express the MuSK antigen on their surface to act as a decoy, selectively binding and eliminating only the B cells that express the Anti-MuSK BCR while sparing the healthy B cell population (Cabaletta Bio, 2024). This approach represents a shift toward personalized immunotherapy, aiming to provide a durable clinical remission by removing the underlying cause of autoantibody production without inducing broad systemic immunosuppression (Nature Biotechnology, 2023).

Other names

MuSK-specific B cell receptorMuSK-reactive B cell receptorAnti-MuSK surface immunoglobulinMuSK-binding B cell receptor

Selective depletion of autoreactive B cells through direct binding of a chimeric autoantibody receptor (CAAR) to the surface-expressed anti-MuSK B cell receptor, triggering T cell-mediated cytotoxicity against the specific B cell clone.