Fc receptors: Activation-inhibition receptor pairing
  • Jeffrey V. Ravetch
Conference paper


Cell surface receptors for IgG immune complexes are found on essentially all major subgroups of cells of the immune system, including antigen presenting cells, such as dendritic cells, antibody producing cells, such as B lymphocytes, and effector cells such as macrophages, granulocytes, mast cells and NK cells (Ravetch and Kinet 1991; Daëron 1997; Ravetch and Clynes 1998). Crosslinking of these receptors triggers a wide array of cellular responses which, in concert, contribute significantly to shaping the antibody repertoire, maintaining tolerance and initiating the inflammatory response. The ability to regulate this wide array of biological responses is central to the generation of appropriate immunity in response to challenge by infectious pathogens, senescent cells and neoplasms. The importance of maintaining appropriate responses to immune complexes is revealed by mutations in these pathways which result in the emergence of systemic autoimmunity and autoimmune diseases. The ability to regulate these potent biological systems is achieved by coupling receptors with similar ligand specificity to opposing cellular responses. Thus, immune complexes co-engage both activation (FcγRIII) and inhibitory (FcγRIIB) receptors simultaneously, resulting in a cellular response which reflects the expression levels of each member of the pair (Bolland and Ravetch 1999). In this manner, FcRs are capable of setting thresholds for activation by immune complexes, terminating activation signals and modulating B cell responses during antigen driven affinity maturation.


Immune Complex Antibody Repertoire Antibody Produce Cell Systemic Autoimmunity Arthus Reaction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bolland S, Pearse R, Kurosaki T, Ravetch JV (1998) SHIP modulates immune receptor responses by regulating membrane association of Btk. Immunity 8: 509–516PubMedCrossRefGoogle Scholar
  2. Bolland S, Ravetch JV (1999) Inhibitory pathways triggered by ITIM-containing receptors. Adv Immunol 72: 149–177PubMedCrossRefGoogle Scholar
  3. Bolland S, Ravetch JV (2000) Spontaneous autoimmune disease in FcγRIIB-deficient mice results from strain-specific epistasis. Immunity 13: 277–285PubMedCrossRefGoogle Scholar
  4. Clynes RA, Dumitru C, Ravetch JV (1998) Uncoupling of immune complex formation and kidney damage in autoimmune glomerulonephritis. Science 279: 1052–1054PubMedCrossRefGoogle Scholar
  5. Clynes R, Maizes JS, Guinamard R, Ono M, Takai T, Ravetch JV (1999) Modulation of immune complex induced inflammation in vivo by the coordinate expression of activation and inhibitory Fc receptors. J Exp Med 189: 179–186PubMedCrossRefGoogle Scholar
  6. Clynes R, Ravetch JV (1995) Cytotoxic antibodies trigger inflammation through Fc receptors. Immunity 3: 21–26PubMedCrossRefGoogle Scholar
  7. Clynes R, Takechi Y, Moroi Y, Houghton A, Ravetch JV (1998) Fc receptors are required in passive and active immunity to melanoma. Proc Natl Acad Sci USA 95: 652–656PubMedCrossRefGoogle Scholar
  8. Clynes RA, Towers T, Presta LG, Ravetch JV (2000) Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nature Med 6: 443–446PubMedCrossRefGoogle Scholar
  9. Daëron M (1997) Fc receptor biology. Annu Rev Immunol 15: 203–234PubMedCrossRefGoogle Scholar
  10. Nakamura A, Yuasa T, Ujike A, Ono M, Nukiwa T, Ravetch JV, Takai T (2000) Fcγ receptor IIB-deficient mice develop Goodpasture’s syndrome upon immunization with type IV collagen: A novel murine model for autoimmune glomerular basement membrane disease. J Exp Med 191: 899–906PubMedCrossRefGoogle Scholar
  11. Pearse RN, Kawabe T, Bolland S, Guinamard R, Kurosaki T, Ravetch JV (1999) SHIP recruitment attenuates FcγRIIB-inducedB cell apoptosis. Immunity 10: 753–760PubMedCrossRefGoogle Scholar
  12. Ravetch JV, Clynes RA (1998) Divergent roles for Fc receptors and complement in vivo. Annu Rev Immunol 16: 421–432PubMedCrossRefGoogle Scholar
  13. Ravetch JV, Kinet J-P (1991) Fc receptors. Annu Rev Immunol 9: 457–492PubMedCrossRefGoogle Scholar
  14. Yuasa T, Kubo S, Yoshino T, Ujike A, Matsumura K, Ono M, Ravetch JV, Takai T (1999) Deletion of FcγRIIB renders H-2b mice susceptible to collagen-induced arthritis. J Exp Med 189: 187–194PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2001

Authors and Affiliations

  • Jeffrey V. Ravetch
    • 1
  1. 1.Laboratory of Molecular Genetics and ImmunologyThe Rockefeller UniversityNew YorkUSA

Personalised recommendations