Antigen-specific B lymphocytes producing anti-thyroid stimulating hormone receptor (TSHR) autoantibodies (TSHR-specific B cells)

Antigen-specific B lymphocytes producing anti-thyroid stimulating hormone receptor (TSHR) autoantibodies are the pathogenic drivers of Graves' disease (Smith & Hegedüs, 2016). These cells express B-cell receptors (BCRs) that recognize the TSHR, leading to their activation and differentiation into autoantibody-secreting plasma cells (McLachlan & Rapoport, 2013). The resulting autoantibodies, known as thyroid-stimulating immunoglobulins (TSI), mimic the action of TSH, causing overproduction of thyroid hormones and thyroid gland enlargement (Davies et al., 2020). Targeting this specific subset of B cells is a major goal in precision immunology to avoid the broad immunosuppression associated with pan-B-cell depletion like Rituximab (Ellebrecht et al., 2016). Therapeutic approaches include Chimeric Autoantibody Receptor (CAAR) T-cell therapies, which utilize the TSHR protein as an extracellular bait to selectively identify and eliminate TSHR-reactive B cells (Parvathaneni et al., 2022). By removing the source of the autoantibodies, these therapies aim to restore normal thyroid function and treat extrathyroidal manifestations like Graves' ophthalmopathy. This cellular target represents a shift from managing symptoms with antithyroid drugs to addressing the underlying immunological defect.

Other names

TSHR-reactive B cellsThyroid-stimulating hormone receptor-specific B lymphocytesTRAb-producing B cellsTSHR-specific B lymphocytes

Selective depletion of B lymphocytes expressing surface-bound immunoglobulins specific for the thyroid-stimulating hormone receptor (TSHR) through targeted cytotoxicity or immune-mediated clearance.