Demonstration of a severe complement defect in FcRγ-deficient mice (134.63)

Abstract

Abstract Several studies have examined the relative roles of complement vs. Fc receptors (FcRs) in host protection and inflammatory disease. Many of these studies have concluded that the more important role is played by stimulatory Fc receptors. These conclusions were based, however, on the assumption that complement activation occurs normally in the absence of stimulatory Fc receptors. We have used FcRγ-deficient mice, which lack all stimulatory FcRs, to examine this assumption. FcRγ-sufficient and -deficient mice were found to have similar levels of C3 in blood. Also, as expected, similar amounts of IgG2a became associated with blood leukocytes from both mouse strains after intravenous injection of a complement fixing IgG2a mAb to MHC class I Ag. Surprisingly, however, >10-fold more C3 became associated with the blood leukocytes from FcRγ-sufficient mice than those from FcRγ-deficient mice. Additionally, >6-fold more C5a was generated in blood from FcRγ-sufficient than deficient mice. These results demonstrate that mice that lack all stimulatory FcRs have a severe abnormality in complement activation. This abnormality may well contribute to the decreased protective immunity and increased resistance to inflammatory disease characteristic of FcRγ-deficient mice that have previously been ascribed solely to direct effects of the absence of stimulatory FcRs.