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

Pierre Bruhns1, Astrid Samuelsson, Jeffrey W Pollard

  • 1Laboratory of Molecular Genetics and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.

Immunity
|April 23, 2003
PubMed

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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