Redundant and alternative roles for activating Fc receptors and complement in an anti body-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 (FcgammaR gamma(-/-)) and in mice deficient in the C3 complement component. Mice doubly deficient in both FcgammaRgamma and C3 did not develop hypopigmentation, suggesting that complement and FcgammaR formed redundant mechanisms. Following passive immunization with antibody, no further adaptive immune responses were required. Chimeric FcgammaR gamma(-/-),C3(-/-) mice reconstituted with bone marrow from either FcgammaR gamma(-/-) or C3-/- mice or adoptively transferred with FcgammaR gamma(+/-) macrophages did develop antibody-mediated hypopigmentation. Thus, either complement or macrophages expressing activating FcgammaR can independently and alternatively mediate disease in a model of autoimmune vitiligo.