BCRcoreceptor

BCR co-receptor refers to a multi-protein complex that associates with the B cell receptor (BCR) to modulate and amplify signaling during antigen recognition. The primary components of the BCR co-receptor are CD19, CD21 (CR2), and CD81 (TAPA-1). This complex is expressed on mature B cells and interacts with the BCR to tune its response to antigen.

CD21 binds the complement fragment C3d on opsonized antigens, bringing the antigen into close proximity with the BCR. When co-engaged with the BCR, CD21 lowers the activation threshold and strengthens signaling. CD19 serves as the signaling amplifier: its cytoplasmic tail contains tyrosine-based motifs that, when phosphorylated by Src-family kinases, recruit signaling molecules such as PI3K and PLCγ2, enhancing downstream pathways such as PI3K-Akt and Ca2+ flux. CD81 contributes by organizing and stabilizing the complex within membrane microdomains and promoting proper surface expression of CD19 and CD21, facilitating efficient signal propagation.

Functionally, the BCR co-receptor enhances B cell activation, proliferation, and antibody production, and supports germinal center reactions, particularly in response to low-affinity or subthreshold antigens. Clinically, defects or dysregulation of BCR co-receptor signaling can impair humoral immunity and have been linked to autoimmune processes. Therapeutically, CD19-targeted approaches, including monoclonal antibodies and chimeric antigen receptor (CAR) T cells, exploit the dependency of B cells on this signaling axis for effective treatment of certain B cell malignancies.