The Ig-like receptors provide positive and negative regulation of immune cells upon recognition of various ligands, thus enabling those cells to respond adequately to extrinsic stimuli. Murine paired Ig-like receptor (PIR)-A and PIR-B, a typical receptor pair of the Ig-like receptor family, are expressed on a wide range of cells in the immune system, such as B cells, mast cells, macrophages and dendritic cells, mostly in a pair-wise fashion. The PIR-A requires the homodimeric Fc receptor common γ chain for its efficient cell-surface expression and for the delivery of activation signaling. In contrast, PIR-B inhibits receptor-mediated activation signaling in vitro upon engagement with other activating-type receptors, such as the antigen receptor on B cells and the high-affinity Fc receptor for IgE on mast cells. Although the ligands for PIR-A and PIR-B remain unknown, recent studies on PIR-B-deficient mice have provided us with valuable insight into the physiological significance of PIR-B, particularly in its regulatory role in balancing the humoral immune response.