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, a
nd B1 B cell deficiency. IgM receptor-induced Ca2+ flux and proliferation t
o 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/Bln
k 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 transd
uction pathway broadly utilized by immunoglobulin superfamily receptors.