CD72. a type II transmembrane protein belonging to the C-type lectin family, is predominantly expressed on B cells and serves as a co-receptor for B-cell receptor (BCR) signaling. It contains an extracellular C-type lectin domain, a transmembrane region, and a cytoplasmic tail with immunoreceptor tyrosine-based inhibitory motifs (ITIMs). CD72 interacts with its ligand CD100 (SEMA4D), modulating immune responses by balancing activating and inhibitory signals. While CD72 generally acts as a negative regulator of B-cell activation, its role is context-dependent, influencing processes like apoptosis, proliferation, and tolerance.
Research highlights CD72's involvement in autoimmune diseases and malignancies. In systemic lupus erythematosus (SLE), altered CD72 expression correlates with B-cell hyperactivity, suggesting its regulatory dysfunction contributes to autoimmunity. Conversely, CD72 is overexpressed in certain B-cell lymphomas but downregulated in chronic lymphocytic leukemia (CLL), indicating disease-specific roles. CD72 antibodies, particularly monoclonal antibodies (mAbs), have emerged as tools for studying these mechanisms and developing targeted therapies. Some anti-CD72 mAbs show potential in inducing apoptosis in malignant B cells or modulating immune checkpoints. Additionally, CD72-targeting antibody-drug conjugates (ADCs) and bispecific antibodies are being explored for cancer immunotherapy. As a relatively understudied target compared to CD19 or CD20. CD72 offers alternative therapeutic avenues, especially in resistant or relapsed cases. Ongoing studies aim to clarify its precise signaling mechanisms and optimize antibody-based interventions.