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The immune response to apoptotic cells.

D Mevorach1

  • 1Laboratory for Cellular and Molecular Immunology, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Israel. mevdm@netvision.net.il

Annals of the New York Academy of Sciences
|February 11, 2000
PubMed
Summary

Excessive or improperly processed apoptotic cells can trigger autoimmune responses, leading to conditions like lupus. This study shows how cell death remnants can generate autoantibodies in mice.

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Area of Science:

  • Immunology
  • Cell Biology
  • Autoimmunity

Background:

  • Programmed cell death (PCD) involves cell killing and subsequent removal by phagocytes.
  • Normally, phagocytes do not mount inflammatory responses or produce autoantibodies against apoptotic cells.
  • Apoptotic cells expose self-antigens on their surface, like nucleosomes.

Purpose of the Study:

  • To investigate if excess or abnormally processed apoptotic cells can induce autoantibody production.
  • To understand the mechanisms behind autoantigen presentation and immune response.

Main Methods:

  • Induction of syngeneic apoptotic cell load in normal mice.
  • Monitoring for hypergammaglobulinemia, specific autoantibodies (anti-DNA, anticardiolipin), and glomerular deposition.
  • Analysis of apoptotic cell uptake mechanisms, including complement involvement.

Main Results:

  • Syngeneic apoptotic load induced transient hypergammaglobulinemia and autoantibodies against DNA and cardiolipin in mice.
  • Glomerular depositions were observed in mice subjected to apoptotic load.
  • Complement-mediated opsonization is a key mechanism for apoptotic cell uptake.

Conclusions:

  • Aberrant handling of apoptotic cells, potentially due to complement deficiencies, can lead to immunogenicity.
  • The immunogenicity of apoptotic cells may explain autoantigen selection in autoimmune diseases like systemic lupus erythematosus (SLE).

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