Anti-desmoglein 3-specific B cell receptor (DSG3-BCR)

The anti-desmoglein 3-specific B cell receptor is a membrane-bound immunoglobulin expressed on the surface of pathogenic, autoreactive B cells in patients with pemphigus vulgaris (PV) (Ellebrecht et al., 2016). This receptor specifically recognizes desmoglein 3 (DSG3), a critical cell-cell adhesion protein in the desmosomes of the skin and mucous membranes (Payne et al., 2019). Binding of DSG3 to these receptors triggers B cell differentiation into plasma cells that secrete anti-DSG3 IgG autoantibodies, which cause the loss of keratinocyte adhesion (acantholysis) and subsequent blistering. Modern therapeutic approaches, such as DSG3-CAART, utilize the DSG3 protein itself as the extracellular domain of a chimeric receptor on T cells to selectively target and destroy these specific B cells (Lee et al., 2020). This precision therapy aims to eliminate the source of pathogenic autoantibodies without the broad immunosuppression associated with traditional treatments like corticosteroids or anti-CD20 therapies.

Other names

Desmoglein 3-specific B-cell receptorDSG3-reactive B-cell receptorAnti-DSG3 BCRPemphigus vulgaris B-cell receptor

Selective depletion of autoreactive B cells through Chimeric Autoantibody Receptor (CAAR) T-cell mediated cytotoxicity, where the CAAR T cell expresses the DSG3 extracellular domain to bind and kill B cells expressing anti-DSG3 BCRs (Ellebrecht et al., 2016).