Anti-desmoglein 1 and desmoglein 3 dual-specific B cell receptors (DSG1/DSG3 BCRs)

Anti-desmoglein 1 (DSG1) and desmoglein 3 (DSG3) dual-specific B cell receptors (BCRs) are the molecular signatures of the autoreactive B cell clones responsible for the pathogenesis of pemphigus, a group of life-threatening autoimmune blistering diseases (Lee et al., JCI Insight, 2020). These BCRs are membrane-bound immunoglobulins expressed on the surface of B cells that recognize desmogleins, which are cadherin-type cell adhesion molecules essential for maintaining the structural integrity of the epidermis and mucous membranes. In patients with pemphigus vulgaris and pemphigus foliaceus, B cells expressing these receptors undergo activation and differentiation into plasma cells that secrete pathogenic autoantibodies, causing loss of cell-to-cell adhesion known as acantholysis. These specific BCRs serve as the primary targets for Chimeric Autoantibody Receptor (CAAR) T-cell therapies, such as DSG3-CAART, which are designed to selectively eliminate the pathogenic B cell population while preserving the rest of the immune system (Ellebrecht et al., Science, 2016). By using the DSG protein itself as the targeting domain on the T cell surface, the therapy achieves high precision in identifying and killing only the B cells that possess the corresponding anti-DSG BCRs.

Other names

Desmoglein-specific B cell receptorsAutoreactive B cell receptors in pemphigusDSG1-specific BCRDSG3-specific BCRDSG1/DSG3 dual-reactive B cell receptor

Targeted depletion of autoreactive B cells through Chimeric Autoantibody Receptor (CAAR) T-cell mediated cytotoxicity. CAAR-T cells are engineered to express the extracellular domains of the DSG1 or DSG3 autoantigens, which act as bait to specifically bind the B cell receptors (BCRs) of autoreactive B cells, leading to their selective destruction while sparing healthy B cells (Ellebrecht et al., Science, 2016).