The inhibitory coreceptors CD22 and CD72 downmodulate B-cell receptor (BCR) signaling and function as a molecular switch, determining whether antigen-stimulated B cells undergo apoptosis or proliferation. These coreceptors carry an intrinsic property for associating with the BCR, and this association is crucial for the initiation of signal inhibition through phosphorylation of these coreceptors by BCR-associated kinases. Recent findings have demonstrated that signal inhibition by these coreceptors is regulated by ligands for the coreceptors and by molecules binding to the coreceptors or the BCR. Moreover, signal inhibition by CD22 depends on the BCR isotype. These findings suggest a dynamic regulation of these coreceptors through molecular interactions on the B-cell surface.