Colony-stimulating factor-1-dependent macrophages are responsible for IVIG protection in antibody-induced autoimmune disease.
The ability of IVIG to induce expression of Fc gamma RIIB and thereby prevent antibody-induced inflammation has been used as a probe to dissect the effector cell components in the KRNxNOD (K/BxN) arthritis model. IVIG protection resulted from the induction of Fc gamma RIIB on infiltrating macrophages but not neutrophils, indicating a critical role for macrophage activation in this disease model. Disease induction but not IVIG protection was observed in CSF-1-deficient mice (op/op) in K/BxN arthritis, thus defining different macrophage subsets in these processes. These results suggest a two-step model for IVIG protection in which CSF-1-dependent macrophages act as innate "sensors" for the Fc fragment of IVIG, leading to the induction of Fc gamma RIIB on CSF-1-independent "effector" macrophages thereby raising the threshold required for Fc gamma RIII activation and preventing autoantibody-triggered inflammation.
Bruhns
Pierre
P
Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Samuelsson
Astrid
A
Pollard
Jeffrey W
JW
Ravetch
Jeffrey V
JV
D000818:Animals; D001168:Arthritis / Q000517:prevention & control*; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000517:prevention & control*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000517:prevention & control; D017452:Receptors, IgG / Q000096:biosynthesis
D001323:Autoantibodies; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG; D016173:Macrophage Colony-Stimulating Factor