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Published on: March 25, 2016
Immune complexes inhibit apoptosis of chronic lymphocytic leukaemia B cells
R Gamberale1, J R Geffner, A Trevani
1Laboratory of Immunology, Institute of Haematologic Research, National Academy of Medicine, Buenos Aires, Argentina.
Insights
Immune complexes (IC) prevent apoptosis in chronic lymphocytic leukemia (B-CLL) B cells by engaging accessory immune cells. This effect, partly mediated by IFN-gamma release, also increases HLA-DR expression on B-CLL cells.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Chronic lymphocytic leukemia (B-CLL) is a B-cell malignancy.
- Understanding factors influencing B-CLL cell survival is crucial for treatment strategies.
Purpose of the Study:
- To investigate the impact of immune complexes (IC) on the apoptosis of B-CLL cells.
- To elucidate the mechanisms underlying IC-mediated modulation of B-CLL cell survival.
Main Methods:
- Incubation of B-CLL cells with various forms of IC (pIC, E-IgG, aIgG).
- Assessment of spontaneous and drug-induced apoptosis.
- Depletion of accessory immune cells (T lymphocytes, monocytes, NK cells).
- Use of neutralizing anti-IFNgamma monoclonal antibodies (MoAb).
- Analysis of HLA-DR expression on B-CLL cells.
Main Results:
- IC significantly inhibited spontaneous and chemotherapy-induced apoptosis of B-CLL cells.
- The anti-apoptotic effect of IC was dependent on the presence of accessory leucocytes.
- IFN-gamma released by non-malignant cells contributed to the IC-mediated inhibition of apoptosis.
- IC treatment led to increased HLA-DR expression on B-CLL cells, indicating cellular activation.
Conclusions:
- Immune complexes protect B-CLL cells from apoptosis through interactions with accessory immune cells.
- IFN-gamma plays a partial role in mediating these protective effects.
- IC-induced apoptosis inhibition is associated with B-CLL cell activation, evidenced by increased HLA-DR expression.
Abstract:
In the present study we examined the effect of immune complexes (IC) on the survival of chronic lymphocytic leukaemia (B-CLL) B cells. Our results showed that either precipitating IC (pIC), Ab-coated erythrocytes (E-IgG) or heat-aggregated IgG (aIgG) significantly inhibited spontaneous apoptosis of B-CLL cells, as well as that induced by fludarabine, chlorambucil or dexamethasone. After depletion of T lymphocytes, monocytes and NK cells, incubation with IC was no longer able to delay B-CLL cells apoptosis, suggesting that prevention of apoptosis depends on IC interaction with accessory leucocytes. The release of IFNgamma by non-malignant cells upon activation with IC was responsible, to some extent, for IC effects as shown by the fact that neutralizing anti-IFNgamma MoAb partially prevented their ability to inhibit B-CLL cells apoptosis. The observation that treatment with IC resulted in increased expression of HLA-DR on B-CLL cells suggests that inhibition of apoptosis is associated with cellular activation.
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