B-chronic lymphocytic leukemia cells and other B cells can produce granzyme B and gain cytotoxic potential after interleukin-21-based activation
| Autor: | James E. Wooldridge, Bernd Jahrsdörfer, Sue E. Blackwell, Christiana M. Taylor, George J. Weiner, Melinda W. Andreski, Jian Huang, Laura S. Jacobus |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
CpG Oligodeoxynucleotide
Chronic lymphocytic leukemia Immunology Apoptosis Biology In Vitro Techniques Lymphocyte Activation Biochemistry Granzymes Interleukin 21 Immune system Lysosomal-Associated Membrane Protein 1 hemic and lymphatic diseases medicine Tumor Cells Cultured Cytotoxic T cell Humans Cells Cultured Immunobiology B-Lymphocytes Interleukins Serine Endopeptidases Interleukin-21 Receptor alpha Subunit Cell Biology Hematology Receptors Interleukin medicine.disease Leukemia Lymphocytic Chronic B-Cell Recombinant Proteins Up-Regulation B-1 cell Granzyme B Granzyme Oligodeoxyribonucleotides biology.protein Cancer research Receptors Interleukin-21 T-Lymphocytes Cytotoxic |
| Popis: | B cells currently are not viewed as being capable of producing granzyme B or being cytotoxic. We found that B-chronic lymphocytic leukemia (B-CLL) cells treated with interleukin-21 (IL-21) produce low levels of granzyme B. The addition of either CpG oligodeoxynucleotide (ODN) or anti-B-cell-receptor antibody (anti-BCR) to IL-21 results in enhanced production of functional granzyme B by B-CLL cells. B-CLL cells treated with IL-21 and CpG ODN undergo apoptosis and are able to induce apoptosis of untreated bystander B-CLL cells. This effect can be inhibited by anti-granzyme B antibody. Benign human B cells, Epstein-Barr virus (EBV)-transformed lymphoblasts, and many standard lymphoma cell lines produce high levels of granzyme B in response to IL-21 and anti-BCR. Our results suggest that the ability to induce production of functional granzyme B by B cells could open new approaches to the therapy of B-CLL and other B-cell malignancies. Our findings also have significant implications for our understanding of the role of B cells for immune regulation and for a variety of immune phenomena, including cancer immunity, autoimmunity, and infectious immunity. |
| Databáze: | OpenAIRE |
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