Complement activation by both classical and alternative pathways is critical for the effector phase of arthritis

Eur J Immunol. 2004 Apr;34(4):1208-16. doi: 10.1002/eji.200424895.


To analyze the role of the classical and alternative pathways of complement activation in the effector phase of arthritis, we have induced arthritis in C3- and factor B (FB)-deficient (C3(-/-) and FB(-/-)) DBA/1J mice using well-defined monoclonal IgG2b and IgG2a antibodies to type II collagen. In control DBA/1J mice, severe swelling of the joints, destruction of cartilage and erosion of bone developed very rapidly with a 100% incidence and a peak on days 7-10. Although 75% of C3(-/-) mice developed arthritis, the clinical severity was very mild and the onset was delayed. Severity of arthritis in FB(-/-) mice ranked intermediate in comparison with C3(-/-) and control mice with an incidence of 100%. Immunohistochemical analysis of the inflamed joints demonstrated substantial reduction in macrophage and neutrophilic leukocyte infiltration in both C3(-/-) and FB(-/-) mice, thereby confirming the clinical findings. We conclude that both the classical and the alternative pathways of complement activation are involved in the effector phase of arthritis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / pathology
  • Complement Activation / immunology*
  • Complement C3 / deficiency
  • Complement Factor B / deficiency
  • Complement Pathway, Alternative*
  • Complement Pathway, Classical*
  • Enzyme-Linked Immunosorbent Assay
  • Immunohistochemistry
  • Inflammation / immunology
  • Inflammation / pathology
  • Joints / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Monocytes / immunology
  • Monocytes / pathology
  • Neutrophils / immunology
  • Neutrophils / pathology


  • Complement C3
  • Complement Factor B