Phospholipase Cγ2 is essential in the functions of B cell and several Fc receptors

Many receptors activate phospholipase C gamma 1 or -gamma 2. To assess the role of PLC gamma 2, 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 PLC gamma 2 is downstream in Btk/Blnk signaling. FcR gamma signaling is also defective, resulting in a loss of collagen-induced platelet aggregation, mast cell Fc epsilon R function, and NK cell Fc gamma RIII and 2B4 function. The results define a signal transduction pathway broadly utilized by immunoglobulin superfamily receptors.