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

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Abstract
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.