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

Immunity. 2003 Apr;18(4):573-81. doi: 10.1016/s1074-7613(03)00080-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arthritis / prevention & control*
  • Autoantibodies / immunology*
  • Autoimmune Diseases / prevention & control*
  • Immunoglobulins, Intravenous / therapeutic use*
  • Macrophage Colony-Stimulating Factor / physiology*
  • Macrophages / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Purpura, Thrombocytopenic, Idiopathic / prevention & control
  • Receptors, IgG / biosynthesis


  • Autoantibodies
  • Immunoglobulins, Intravenous
  • Receptors, IgG
  • Macrophage Colony-Stimulating Factor