Role of Complement-Binding CD21/CD19/CD81 in Enhancing Human B Cell Protection from Fas-Mediated Apoptosis
| العنوان: | Role of Complement-Binding CD21/CD19/CD81 in Enhancing Human B Cell Protection from Fas-Mediated Apoptosis |
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| المؤلفون: | Rasem J. Fattah, Patricia K. A. Mongini, Sonia Tolani, Anna E. Jackson, John K. Inman |
| المصدر: | The Journal of Immunology. 171:5244-5254 |
| بيانات النشر: | The American Association of Immunologists, 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | Apoptosis, Ligands, Fas ligand, TNF-Related Apoptosis-Inducing Ligand, hemic and lymphatic diseases, Immunology and Allergy, Child, Cells, Cultured, B-Lymphocytes, Caspase 8, Membrane Glycoproteins, Intracellular Signaling Peptides and Proteins, breakpoint cluster region, Antibodies, Monoclonal, Nuclear Proteins, Complement C3, Cell biology, medicine.anatomical_structure, Proto-Oncogene Proteins c-bcl-2, Caspases, Child, Preschool, Co-Repressor Proteins, Protein Binding, Fas Ligand Protein, Adolescent, Cell Survival, Macromolecular Substances, Antigens, CD19, CD40 Ligand, Immunology, bcl-X Protein, Receptors, Antigen, B-Cell, Caspase 3, DNA Fragmentation, Biology, CD19, Tetraspanin 28, Adjuvants, Immunologic, Antigens, CD, medicine, Humans, fas Receptor, CD40 Antigens, B cell, Adaptor Proteins, Signal Transducing, Binding Sites, Tumor Necrosis Factor-alpha, Membrane Proteins, Cancer research, biology.protein, Receptors, Complement 3d, Apoptosis Regulatory Proteins, Carrier Proteins, Molecular Chaperones, CD81 |
| الوصف: | Defective expression of Fas leads to B cell autoimmunity, indicating the importance of this apoptotic pathway in eliminating autoreactive B cells. However, B cells with anti-self specificities occasionally escape such regulation in individuals with intact Fas, suggesting ways of precluding this apoptosis. Here, we examine whether coligation of the B cell Ag receptor (BCR) with the complement (C3)-binding CD21/CD19/CD81 costimulatory complex can enhance the escape of human B cells from Fas-induced death. This was warranted given that BCR-initiated signals induce resistance to Fas apoptosis, some (albeit not all) BCR-triggered events are amplified by coligation of BCR and the co-stimulatory complex, and several self Ags targeted in autoimmune diseases effectively activate complement. Using a set of affinity-diverse surrogate Ags (receptor-specific mAb:dextran conjugates) with varying capacity to engage CD21, it was established that BCR:CD21 coligation lowers the BCR engagement necessary for inducing protection from Fas apoptosis. Enhanced protection was associated with altered expression of several molecules known to regulate Fas apoptosis, suggesting a unique molecular model for how BCR:CD21 coligation augments protection. BCR:CD21 coligation impairs the generation of active fragments of caspase-8 via dampened expression of membrane Fas and augmented expression of FLIPL. This, in turn, diminishes the generation of cells that would be directly triggered to apoptosis via caspase-8 cleavage of caspase 3 (type I cells). Any attempt to use the mitochondrial apoptotic protease-activating factor 1 (Apaf-1)-dependent pathway for apoptosis (as type II cells) is further blocked because BCR:CD21 coligation promotes up-regulation of the mitochondrial antiapoptotic molecule, Bcl-2. |
| تدمد: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.171.10.5244 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2a475e3a8ee5fd656ace57d4eb8e3f55 https://doi.org/10.4049/jimmunol.171.10.5244 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2a475e3a8ee5fd656ace57d4eb8e3f55 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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| DOI: | 10.4049/jimmunol.171.10.5244 |