B-cell receptor (BCR) (BCR)

The B-cell receptor (BCR) on autoreactive B lymphocytes is a specialized transmembrane protein complex that recognizes self-antigens, triggering pathological immune responses [1, 2]. It consists of a surface-bound immunoglobulin (sIg) molecule associated with the CD79A (Ig-alpha) and CD79B (Ig-beta) signaling subunits [1, 3]. In autoimmune conditions like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), these receptors escape central and peripheral tolerance mechanisms, allowing the B cells to proliferate and differentiate into autoantibody-secreting plasma cells [4, 5]. Targeting the BCR pathway is a major therapeutic strategy, utilizing inhibitors of downstream kinases such as Bruton's tyrosine kinase (BTK) and Spleen tyrosine kinase (Syk) to disrupt signaling [6, 7]. Additionally, novel Chimeric Autoantibody Receptor (CAAR) T-cell therapies are being designed to specifically bind to and eliminate B cells expressing these autoreactive receptors, providing a highly selective approach to treating autoimmune diseases [8].

Other names

Surface immunoglobulinsIgAntigen receptor complexB-cell antigen receptorAutoreactive B-cell receptor

Inhibition of downstream signaling kinases (BTK, Syk), depletion of B-cells expressing the receptor via monoclonal antibodies, or direct selective elimination of autoreactive B-cells by engineered CAAR T-cells.