Submitted March 30, 2006
Accepted June 13, 2006
B-Chronic Lymphocytic Leukemia Cells and other B cells can produce Granzyme B and gain cytotoxic potential after Interleukin-21-based activation
Bernd Jahrsdorfer, Sue E Blackwell, James E Wooldridge, Jian Huang, Melinda W Andreski, Laura S Jacobus, Christiana M Taylor, and George J Weiner*
Holden Comprehensive Cancer Center, University of Iowa, USA
Department of Statistics, University of Iowa, USA
* Corresponding author; email: george-weiner{at}uiowa.edu.
B cells are not currently 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 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, EBV-tranformed lymphoblasts, and many standard lymphoma cell lines produce high levels of granzyme B in response to IL-21 and anti-BCR. Our results suggest 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 on 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.
