Redundant and alternative roles for activating Fc receptors and complement in an antibody-dependent model of autoimmune vitiligo.
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.
The Swim Across America Laboratory, Memorial Sloan-Kettering Cancer Center and Weill Graduate School of Cornell University, New York, NY 10021, USA.
Jiri
J
Trcka
Yoichi
Y
Moroi
Raphael A
RA
Clynes
Stacie M
SM
Goldberg
Amy
A
Bergtold
Miguel Angel
MA
Perales
Minghe
M
Ma
Cristina R
CR
Ferrone
Michael C
MC
Carroll
Jeffrey V
JV
Ravetch
Alan N
AN
Houghton
D019264:Adoptive Transfer; D000818:Animals; D003167:Complement Activation / Q000502:physiology*; D003176:Complement C3 / Q000276:immunology; D005838:Genotype; D007116:Immunization, Passive; D008264:Macrophages / Q000276:immunology; D008544:Melanocytes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010088:Oxidoreductases; D011961:Receptors, Fc / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014820:Vitiligo / Q000276:immunology*
D003176:Complement C3; D008562:Membrane Glycoproteins; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse