Low affinity immunoglobulin gamma Fc receptor IIb (CD32B) and B-cell antigen receptor complex-associated protein beta chain (CD79B) (CD32B/CD79B)

CD32B (Fc gamma receptor IIb) and CD79B (part of the B-cell receptor complex) are co-targeted on B cells to modulate immune responses in autoimmune diseases (UniProt: P31994, P40259). CD32B is the only inhibitory Fc gamma receptor, containing an immunoreceptor tyrosine-based inhibition motif (ITIM) that naturally dampens B-cell activation. CD79B is a critical signaling component of the B-cell receptor (BCR) complex, essential for B-cell activation and proliferation. In diseases like systemic lupus erythematosus (SLE), B-cell hyperactivity leads to the production of pathogenic autoantibodies and tissue damage (PubMed: 35058315). Therapeutic agents, such as the bispecific DART molecule PRV-3279, are designed to co-engage these two proteins to mimic the natural inhibitory feedback loop of the immune system (PubMed: 21149515). This co-engagement recruits phosphatases to the BCR complex, effectively inhibiting B-cell signaling, proliferation, and the production of autoantibodies. Unlike traditional B-cell depleting therapies, this approach aims to regulate B-cell function while maintaining the B-cell population, potentially offering a more favorable safety profile. By specifically targeting the activation threshold of B cells, these therapies can intercept the pathophysiology of B-cell mediated diseases and potentially reduce the immunogenicity of other biotherapeutics (Provention Bio).

Other names

FCGR2B and CD79BFc gamma receptor IIb and Ig-betaCD32B/CD79B co-targetMGD010 targetCD79B and CD32B

Simultaneous engagement of the inhibitory receptor CD32B and the B-cell receptor component CD79B to trigger CD32B-mediated inhibitory signaling, thereby suppressing B-cell activation and autoantibody production without causing B-cell depletion.