Nucleosomes are exposed at the cell surface in apoptosis

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Apoptotic cells are implicated as a source of autoantigens in systemic lupus erythematosus (SLE).
• The precise role of apoptotic cells in initiating or sustaining the immune response, particularly autoantibody production, remains unclear.
• Understanding these interactions is crucial for developing targeted therapies for autoimmune diseases.

Purpose of the Study:

• To investigate the binding patterns of various autoantibodies to apoptotic cells.
• To elucidate the mechanisms by which nucleosomes are released and exposed during apoptosis.
• To determine the role of nucleosomes in regulating anti-nuclear autoantibody production.

Main Methods:

• Characterization of monoclonal autoantibody binding to apoptotic cells using confocal microscopy.
• Analysis of epitope localization (cytoplasmic and cell surface) during apoptosis.
• Assessment of autoantibody precipitation of histone-DNA complexes from cell cytosol post-apoptosis induction.

Main Results:

• Autoantibodies exhibited specific binding patterns to apoptotic cells, targeting DNA, histones, and nucleosomes.
• Immunoreactive epitopes were found in the cytoplasm and on the cell surface in a caspase-dependent manner.
• Nucleosome-specific autoantibodies precipitated histone-DNA complexes from the cytosol, indicating nucleosome release during apoptosis.

Conclusions:

• Nucleosomes are released from the nucleus and exposed on the cell surface during apoptosis through distinct steps.
• Nucleosomes play a direct role in apoptosis execution and clearance.
• These findings highlight nucleosomes as critical regulators of anti-nuclear autoantibody production in SLE.