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Immunity. 2003 Apr;18(4):573-81.

Colony-stimulating factor-1-dependent macrophages are responsible for IVIG protection in antibody-induced autoimmune disease.

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Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.


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.

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