Acetylcholine receptor-specific pathogenic T and B lymphocytes (AChR-specific lymphocytes)

Acetylcholine receptor-specific pathogenic T and B lymphocytes are the specialized immune cell subsets responsible for the development and progression of Myasthenia Gravis (MG) (Gilhus et al., 2019, Nature Reviews Disease Primers). These B cells differentiate into plasma cells that secrete high-affinity autoantibodies against the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction, while the T cells provide the necessary cytokine environment and MHC-restricted help for B cell maturation and class switching (PubMed: 26836333). The interaction between these cells leads to the destruction of the postsynaptic membrane, resulting in muscle weakness and fatigue. Modern therapeutic interventions, such as Chimeric Autoantibody Receptor (CAAR) T cells and antigen-specific tolerogens, are being developed to selectively deplete or silence these specific clones (Ellebrecht et al., 2016, Science). By targeting only the autoreactive cells, these therapies aim to provide a precision medicine approach that avoids the systemic side effects associated with broad-spectrum corticosteroids and immunosuppressive drugs (Cartesian Therapeutics, 2024). This cellular target represents a shift from broad immunosuppression to antigen-specific immunotherapy in the treatment of autoimmune disorders.

Other names

AChR-reactive T cellsAChR-specific B cellsAnti-AChR B cellsAutoreactive AChR-specific lymphocytesAChR-reactive lymphocytes

Selective depletion of B-cell clones expressing anti-AChR antibodies via chimeric autoantibody receptors or induction of immune tolerance in AChR-reactive T-cells using antigen-specific tolerogens.