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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2712-2719.
Prepublished online as a Blood First Edition Paper on June 29, 2006; DOI 10.1182/blood-2006-03-014001.


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IMMUNOBIOLOGY

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

Bernd Jahrsdörfer, Sue E. Blackwell, James E. Wooldridge, Jian Huang, Melinda W. Andreski, Laura S. Jacobus, Christiana M. Taylor, and George J. Weiner

From the Department of Internal Medicine, The Holden Comprehensive Cancer Center; and Department of Statistics, University of Iowa, Iowa City.

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.


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