B-chronic lymphocytic leukemia cells and other B cells can produce granzyme B and gain cytotoxic potential after interleukin-21-based activation

• Published in: Blood Vol. 108; no. 8; pp. 2712 - 2719
• Main Authors: Jahrsdörfer, Bernd, Blackwell, Sue E., Wooldridge, James E., Huang, Jian, Andreski, Melinda W., Jacobus, Laura S., Taylor, Christiana M., Weiner, George J.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.10.2006; The Americain Society of Hematology; 2006 by The American Society of Hematology
• Subjects: Apoptosis - drug effects; B-Lymphocytes - drug effects; B-Lymphocytes - enzymology; B-Lymphocytes - immunology; Biological and medical sciences; Cells, Cultured; Granzymes; Hematologic and hematopoietic diseases; Humans; Immunobiology; In Vitro Techniques; Interleukin-21 Receptor alpha Subunit; Interleukins - pharmacology; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - enzymology; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocyte Activation - drug effects; Lysosomal-Associated Membrane Protein 1 - metabolism; Medical sciences; Oligodeoxyribonucleotides - pharmacology; Receptors, Interleukin - genetics; Receptors, Interleukin-21; Recombinant Proteins - pharmacology; Serine Endopeptidases - biosynthesis; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - enzymology; T-Lymphocytes, Cytotoxic - immunology; Tumor Cells, Cultured; Up-Regulation - drug effects; Human; Serine endopeptidases; Enzyme; Cytotoxicity; B cell neoplasm; Malignant hemopathy; Immune regulation; B-Lymphocyte; Peptidases; Chronic lymphocytic leukemia; Granzyme B; Interleukin 21; Hydrolases
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-03-014001

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.