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Divergent roles for Fc receptors and complement in vivo
1Laboratory of Molecular Genetics and Immunology, Rockefeller University, New York, NY 10021, USA. ravetch@rockvax.rockefeller.edu
Abstract:
Recent results obtained in mice deficient in either FcRs or complement have revealed distinct functions for these two classes of molecules. While each is capable of interacting with antibodies or immune complexes, the two systems mediate distinct biological effector responses. Complement-deficient mice are unable to mediate innate immune responses to several bacterial pathogens and bacterial toxins, yet respond normally to the presence of cytotoxic antibodies and pathogenic immune complexes. In contrast, FcR-deficient mice display no defects in innate immunity or susceptibility to a variety of pathogens, yet they are unable to mediate inflammatory responses to cytotoxic IgG antibodies or IgG immune complexes, despite the presence of a normal complement system. These results lead to the surprising conclusion that these two systems have evolved distinct functions in host immunity, with complement and its receptors mediating the interaction of natural antibodies (IgM) with pathogens to effect protection, while FcRs couple the interaction of IgG antibodies to effector cells to trigger inflammatory sequelae. These results necessitate a fundamental revision of the role of these antibody-binding systems in the immune response.
Insights
Complement and Fc receptors have distinct roles in immunity. Complement aids natural antibodies against pathogens, while Fc receptors link IgG antibodies to effector cells for inflammation, revising our understanding of antibody-mediated immunity.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Fc receptors (FcRs) and complement systems interact with antibodies and immune complexes.
- Distinct biological effector responses are mediated by FcRs and complement.
Purpose of the Study:
- To elucidate the distinct functions of FcRs and complement in host immunity.
- To understand the specific roles of these systems in response to antibodies and pathogens.
Main Methods:
- Comparative analysis of mice deficient in FcRs or complement.
- Assessment of immune responses to bacterial pathogens, toxins, cytotoxic antibodies, and immune complexes.
Main Results:
- Complement-deficient mice show impaired innate immunity to pathogens but normal responses to cytotoxic antibodies.
- FcR-deficient mice exhibit normal innate immunity but lack inflammatory responses to IgG antibodies and immune complexes.
- These findings highlight separate roles for complement and FcRs in antibody-mediated immunity.
Conclusions:
- Complement and its receptors mediate natural antibody (IgM) interactions with pathogens for protection.
- FcRs couple IgG antibodies to effector cells, initiating inflammatory responses.
- A fundamental revision of antibody-binding systems in immunity is necessitated by these findings.