1. Redundant and alternative roles for activating Fc receptors and complement in an antibody-dependent model of autoimmune vitiligo
- Author
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Jeffrey V. Ravetch, Miguel-Angel Perales, Cristina R. Ferrone, Stacie M. Goldberg, Yoichi Moroi, Minghe Ma, Jiri Trcka, Alan N. Houghton, Raphael Clynes, Michael C. Carroll, and Amy Bergtold
- Subjects
Adoptive cell transfer ,Genotype ,Melanosome membrane ,Recombinant Fusion Proteins ,Immunology ,Fc receptor ,Vitiligo ,Receptors, Fc ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,medicine ,Immunology and Allergy ,Animals ,Receptor ,Complement Activation ,030304 developmental biology ,Hypopigmentation ,Mice, Knockout ,0303 health sciences ,Membrane Glycoproteins ,biology ,Macrophages ,Immunization, Passive ,Complement C3 ,Molecular biology ,Adoptive Transfer ,3. Good health ,Mice, Inbred C57BL ,Infectious Diseases ,biology.protein ,Melanocytes ,medicine.symptom ,Antibody ,Oxidoreductases ,030215 immunology ,Gamma subunit - Abstract
Complement and Fc receptor (FcR)-positive cells mediate effector functions of antibodies. Antibody-dependent immunity against the melanosome membrane glycoprotein gp75/tyrosinase-related protein-1 (TYRP-1) of melanocytes leads to autoimmune hypopigmentation (vitiligo) in mice. Hypopigmentation occurred in mice deficient in activating FcR containing the common gamma subunit (Fc gamma R gamma(-/-)) and in mice deficient in the C3 complement component. Mice doubly deficient in both Fc gamma R gamma and C3 did not develop hypopigmentation, suggesting that complement and Fc gamma R formed redundant mechanisms. Following passive immunization with antibody, no further adaptive immune responses were required. Chimeric Fc gamma R gamma(-/-),C3(-/-) mice reconstituted with bone marrow from either Fc gamma R gamma(-/-) or C3(-/-) mice or adoptively transferred with Fc gamma R gamma(+/-) macrophages did develop antibody-mediated hypopigmentation. Thus, either complement or macrophages expressing activating Fc gamma R can independently and alternatively mediate disease in a model of autoimmune vitiligo.
- Published
- 2002