Autoantigen-specific B-cell receptor (BCR)

The autoantigen-specific B-cell receptor (BCR) is a membrane-bound immunoglobulin expressed on the surface of autoreactive B cells that recognizes and binds to self-antigens. In healthy individuals, these cells are typically eliminated or silenced through central and peripheral tolerance mechanisms; however, their persistence and activation lead to the production of pathogenic autoantibodies and the development of autoimmune diseases (Parvathaneni & Knight, 2023, Front Immunol). Unlike broad B-cell depletion therapies such as anti-CD20 antibodies, targeting the specific BCR allows for the selective elimination of disease-causing B-cell clones while preserving the rest of the humoral immune system. Current therapeutic strategies include Chimeric Autoantibody Receptor (CAAR) T-cell therapy, which engineers T cells to express the autoantigen as an extracellular domain, thereby directing them to kill only the B cells expressing the corresponding autoantigen-specific BCR (Ellebrecht et al., 2016, Science). This approach is being investigated for conditions such as pemphigus vulgaris, where the target is the desmoglein 3-specific BCR, and myasthenia gravis, targeting the MuSK-specific BCR (Oh et al., 2023, Nat Biomed Eng). By focusing on the BCR, these therapies aim to achieve long-term remission without the broad immunosuppression associated with conventional treatments.

Other names

Autoreactive B-cell receptorSelf-reactive B-cell receptorAuto-BCRSurface immunoglobulin on autoreactive B cellsAntigen-specific B-cell receptor

Selective depletion of autoreactive B-cell clones through chimeric autoantibody receptor (CAAR) T-cell mediated cytotoxicity or induction of B-cell anergy via specific antigen binding (Ellebrecht et al., 2016, Science; Lee et al., 2020, JCI).