Harnessing the physiological inhibitory function of FcγRIIb by mAbs that target ITAM receptors has the potential to shut down ITAM‐dependent signaling pathways of major importance in antibody pathologies.32, 108 Such ITAM signaling receptors include the BCR complex on B cells which is active in systemic lupus erythematosus, the FcεRI on basophils and mast cell subsets in allergies or the activating‐type FcγR on a variety of innate leukocytes in antibody‐mediated tissue destruction. In such scenarios, the ITAM signaling receptor complex that is targeted by the therapeutic mAb must be co‐expressed on the cell surface with the inhibitory FcγRIIb. This permits coengagement with ITAM signaling receptor by the Fab of the mAb and inhibitory FcγRIIb by its Fc which is the critical requirement in the inhibitory MOA for such therapeutic mAbs (Figure 1).