Abstract

Many receptors activate phospholipase Cγ1 or -γ2. To assess the role of PLCγ2, we derived enzyme-deficient mice. The mice are viable but have decreased mature B cells, a block in pro-B cell differentiation, and B1 B cell deficiency. IgM receptor–induced Ca2+ flux and proliferation to B cell mitogens are absent. IgM, IgG2a, and IgG3 levels are reduced, and T cell–independent antibody production is absent. The similarity to Btk- or Blnk-deficient mice demonstrates that PLCγ2 is downstream in Btk/Blnk signaling. FcRγ signaling is also defective, resulting in a loss of collagen-induced platelet aggregation, mast cell FcεR function, and NK cell FcγRIII and 2B4 function. The results define a signal transduction pathway broadly utilized by immunoglobulin superfamily receptors.