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Lymphocyte programmed cell death is mediated via HLA class II DR
J P Truman1, M L Ericson, C J Choqueux-Séébold
1Laboratoire d'Immunogénétique Moleculaire, Institut Biomédical des Cordeliers, Paris, France.
International Immunology
|June 1, 1994
Summary
Stimulating human lymphocytes via HLA-DR molecules rapidly induces cell death in activated B cells, distinct from apoptosis. This pathway removes lymphocytes post-immune response, preventing inflammation and optimizing immune interactions.
Area of Science:
- Immunology
- Cell Biology
Background:
- Human Leukocyte Antigen (HLA) class II molecules are crucial for immune responses.
- These molecules are expressed on B lymphocytes and induced on T lymphocytes upon activation.
Purpose of the Study:
- To investigate the effects of stimulating lymphocytes via HLA class II molecules.
- To characterize the mechanism and nature of observed cell death.
Main Methods:
- Lymphocyte stimulation via HLA class II DR, DP, and DQ molecules.
- Analysis of cell death using propidium iodide fluorescence, DNA fragmentation, and cell morphology.
- Investigation of factors like Fc receptors, complement, cytoskeletal integrity, and enzyme activity.
Main Results:
- Stimulation via HLA-DR, but not DP or DQ, induced rapid cell death in up to 60% of lymphocytes.
- A specific sub-population of activated B cells was sensitive to HLA-DR mediated death; resting B cells were unaffected.
- The cell death pathway required cytoskeletal integrity and specific enzyme activities but did not exhibit typical apoptotic DNA fragmentation patterns.
Conclusions:
- HLA class II DR-mediated lymphocyte death is a distinct mechanism, differing from necrosis and apoptosis.
- This process likely serves to eliminate lymphocytes that have completed their immune function, preventing inflammation and facilitating new immune interactions.