Citrullinated antigen-specific B cell receptor (Cit-specific BCR)

The citrullinated antigen-specific B cell receptor (BCR) is the primary antigen-recognition molecule on the surface of B cells that produce anti-citrullinated protein antibodies (ACPAs), which are highly specific biomarkers and pathogenic drivers of rheumatoid arthritis (RA). These BCRs recognize proteins where arginine residues have been post-translationally modified to citrulline, a process catalyzed by peptidylarginine deiminase (PAD) enzymes. In RA, the breach of tolerance to these citrullinated self-antigens leads to the expansion of memory B cells and plasmablasts expressing these specific BCRs, which then secrete ACPAs that form immune complexes and drive chronic synovial inflammation. Therapeutic strategies targeting these BCRs aim to selectively deplete the pathogenic B cell population while sparing the rest of the immune system, thereby avoiding the broad immunosuppression associated with traditional B-cell depleting agents. Emerging approaches include Chimeric Autoantibody Receptor (CAAR) T cells, which express the citrullinated antigen to bait and kill the specific B cells, and CAR-Tregs (Regulatory T cells) engineered with citrullinated antigen-specific receptors to suppress local inflammation.

Other names

ACPA-specific B cell receptorAnti-citrullinated protein antibody-expressing B cell receptorCCP-specific B cell receptorCitrullinated peptide-binding B cell receptorAutoreactive B cell receptor in rheumatoid arthritis

Selective depletion of autoreactive B cells by targeting their unique B-cell receptor (BCR) using antigen-based baits (CAAR-T, antigen-toxin conjugates) or modulation of B-cell activation and tolerance (CAR-Tregs, STALs).