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Dissociation of caspase-mediated events and programmed cell death induced via HLA-DR in follicular lymphoma

Oncogene volume 25, pages 1914–1921 (2006)Cite this article

Abstract

Human leukocyte antigens (HLA) class II antigen-mediated apoptosis has been documented in antigen-presenting cells and B lymphoproliferations. Characteristics of the apoptosis include rapidity and selectivity for mature cells. Follicular lymphomas are particularly refractory to apoptosis. The B-cell lymphoma Ramos shares characteristics of this subgroup and is insensitive to apoptosis via simple HLA-DR engagement. However, oligomerization of HLA-DR antigens induced caspase activation followed by phosphatidylserine externalization, activation of PKC-δ and cleavage of nuclear lamin B. Mitochondrial injury was also detected. However, inhibition of caspase activation simply delayed the apoptotic phenotype but neither protected against cell death nor prevented mitochondrial injury. The data in this report demonstrate that the requirements for the initiating signal (oligomerization versus engagement) as well as the molecular pathways varies between different B lymphoproliferations despite their common expression of HLA-DR. Finally, blockade of caspase activation in parallel with HLA-DR mAb stimulation could provide a potent autovaccination stimulus by leading to necrotic death of B-cell lymphomas.

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Acknowledgements

This work was supported by grants from the Fondation de France, Association pour la recherche contre le Cancer, European Commission Grants QLK362002-01936 and QLRT200202026

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Authors and Affiliations

  1. INSERM Unité 662, Paris, France

    M Carmagnat, D Charron & N A Mooney

  2. AP HP, Hôpital St Louis, Service d'Immunologie et d'Histocompatibilité, Paris, France

    M Carmagnat & D Charron

  3. CHU de Rennes, Hôp Pontchaillou, Laboratoire d’Hématologie, Rennes, France

    B Drénou

  4. Department of Immunology, The Medical School, University of Birmingham, Birmingham, UK

    H Chahal & J M Lord

  5. Institut Pasteur, Unité de Physiopathologie des Infections lentivirales, Paris, France

    J Estaquier

  6. Université Pierre et Marie Curie, Faculté de Médecine, Institut Universitaire d’Hématologie, Centre Hayem, Paris, France

    N A Mooney

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  1. M Carmagnat
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  2. B Drénou
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  4. J M Lord
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Correspondence to N A Mooney.

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Carmagnat, M., Drénou, B., Chahal, H. et al. Dissociation of caspase-mediated events and programmed cell death induced via HLA-DR in follicular lymphoma. Oncogene 25, 1914–1921 (2006). https://doi.org/10.1038/sj.onc.1209222

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