Muscle-specific kinase-specific B cell receptor (MuSK-specific BCR)

The Muscle-specific kinase-specific B cell receptor (MuSK-specific BCR) is a membrane-bound immunoglobulin expressed on the surface of B cells that inappropriately recognize the MuSK protein, a critical receptor tyrosine kinase at the neuromuscular junction (UniProt P57078). In patients with MuSK-associated Myasthenia Gravis (MuSK-MG), these autoreactive B cells differentiate into plasma cells that secrete pathogenic IgG4 autoantibodies, which disrupt the interaction between MuSK and LRP4, leading to severe muscle weakness and respiratory distress (Kohnlein et al., 2023, Journal of Neurology). The MuSK-specific BCR is a primary target for precision medicine, specifically Chimeric AutoAntibody Receptor (CAAR) T-cell therapy, which aims to selectively eliminate only the disease-causing B cells while sparing the rest of the immune system (Cabaletta Bio, 2024). By using the MuSK protein itself as the targeting moiety on engineered T cells, the therapy lures and destroys B cells carrying the MuSK-specific BCR. This approach represents a shift from broad immunosuppression to targeted cellular therapy for autoimmune disorders. Monitoring the reduction of anti-MuSK antibody titers serves as a key clinical biomarker for the efficacy of therapies targeting this receptor.

Other names

MuSK-BCRAnti-MuSK B cell receptorB-cell receptor specific for MuSKMuSK-reactive B cell receptor

Selective depletion of MuSK-specific B cells through Chimeric AutoAntibody Receptor (CAAR) T-cell therapy, where T cells are engineered to express MuSK extracellular domains that bind to and trigger the lysis of B cells expressing the MuSK-specific B cell receptor (Oh et al., 2023, Nature Biotechnology).