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Natural antibodies and autoantibodies bind to injured tissues, activate complement and cause organ damage

Complement traditionally represents the first line of defense against infections. More recently, complement was shown to play a role in shaping the repertoire of the immune response. However, it is well established that uncontrolled and excessive complement activation significantly contributes to diverse pathologies ranging from inflammation, autoimmune tissue injury and injury that follows ischemia, hypoperfusion and reperfusion. In addressing the role of complement in tissue injury, two central questions arise: how is complement activated in each type of injury and to what extent is complement activation responsible for tissue injury? To obtain insight into these questions, we have adopted a mesenteric ischemia/reperfusion (IR) model of tissue injury because the local intestinal damage is associated with complement activation and recruitment and activation of neutrophils. Because immunoglobulin-deficient, RAG-1-/- mice are protected from IR injury and because some Cr2-/- mice have limited numbers of B1 B cells, we asked whether Cr2-/- mice have an altered response to IR injury. Cr2-/- mice are protected from IR injury that is completely restored after injection of normal IgG and IgM. In addition, antibodies with specificities against negatively charged phospholipids and DNA attach to injured tissue and activate complement, resulting in damage. We propose that certain autoantibodies, produced by B1 cells and constituting part of the natural antibody repertoire, bind to cryptic antigens expressed by injured cells and tissues, activate complement and effect tissue damage.

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Tsokos, G., Fleming, S. Natural antibodies and autoantibodies bind to injured tissues, activate complement and cause organ damage. Arthritis Res Ther 6 (Suppl 3), 35 (2004).

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  • Tissue Injury
  • Complement Activation
  • Organ Damage
  • Central Question
  • Injured Tissue