(i) CD20-specific mAb (i.e., rituximab) (anti-CD20), as reported in the current issue of the JCI by Kelishadi et al (7), binds and selectively depletes CD20⁺ B cells, thereby reducing alloantibody levels. Third generation CD20-specific mAbs are under development (e.g., ocrelizumab, ofatumumab). (ii) Inhibitors such as belimumab neutralize BAFF, while inhibitors such as atacicept (TACI-Ig) inhibit both BAFF and APRIL. (iii) Proteasome inhibitors (e.g., bortezomib) reversibly bind to the proteasome and disrupt various cell signaling pathways including the NF-κB pathway. (iv) Complement inhibitors, such as eculizumab (an antibody specific for complement component 5 [C5]), bind the complement protein C5, leading to cessation of complement-mediated cell lysis via the membrane attack complex (MAC). Since activation of the complement system is initiated by binding of 2 alloantibody molecules to a multivalent antigen followed by formation of the C1 complex, C1 inhibitor (C1-INH) prevents initiation of the serial complement cascade by inhibiting proteolytic cleavage of later complement components (specifically C2 and C4) and formation of C3 convertase. (v) Abatacept and belatacept (LEA29Y) are CTLA4-Ig molecules that bind the B7 costimulation molecule and block T cell costimulation of B cell activation and thereby production of alloantibodies. (vi) CD40-specific mAb (anti-CD40) binds the CD40 costimulation molecule. Blocking CD40L/CD40 interactions with CD40-specific antibody prevents T cell help to B cell activation, and consequently alloantibody production is inhibited.