Abstract
IL-21 Plus CpG ODN Induces Granzyme B-Dependent Induction of Apoptosis in CD5-Positive B Cells Including B-CLL Cells
Blood, Vol.108(11), pp.2823-2823
11/16/2006
DOI: 10.1182/blood.V108.11.2823.2823
Abstract
Abstract
Interleukin 21 (IL-21), a recently discovered cytokine with structural homology to IL-2, IL-4 and IL-15, has pleiotropic effects on lymphocyte populations including NK, T and B cells and is currently undergoing early clinical evaluation. We explored the effect of the combination of IL-21 and immunostimulatory CpG ODN on B chronic lymphocytic leukemia (B-CLL), and other CD5-positive B cells. IL-21 plus CpG ODN were synergistic in their ability to induce apoptosis of the B-CLL cells, and also induced production and secretion of granzyme B from the B-CLL cells. B-CLL cells treated with IL-21 and CpG ODN were capable of inducing apoptosis of untreated autologous B-CLL cells. This bystander killing was inhibited by anti-granzyme B antibodies. The effect was observed in all cases of CD5-positive B-CLL, but not in CD5-negative B-CLL samples. IL-21 plus CpG ODN also induced granzyme B production and apoptosis of benign CD5-positive B1 cells obtained from umbilical cord blood. In contrast, the number of CD5-negative B2 cells increased in the same samples during in vitro culture, resulting in a decreased ratio of CD5-positive to CD5-negative cord blood B cells (Fig. 1). Our results indicate the combination of IL-21 and CpG ODN is able to induce apoptosis of both benign and malignant CD5-positive B cells. Given the suspected role of B1 cells in autoimmune diseases, our findings could have important implications for the understanding of their pathogenetic mechanisms. These results might also open new avenues for the development of novel therapies for both autoimmune dieseases and CD5-positive B-CLL.
Figure 1. IL- 21 and CpG ODN therapy selectively eliminates CD5 positive B cells in cord blood. Figure 1. IL- 21 and CpG ODN therapy selectively eliminates CD5 positive B cells in cord blood.
Details
- Title: Subtitle
- IL-21 Plus CpG ODN Induces Granzyme B-Dependent Induction of Apoptosis in CD5-Positive B Cells Including B-CLL Cells
- Creators
- Sue E. Blackwell - University of IowaBernd Jahrsdoerfer - University of IowaJames E. Wooldridge - University of IowaJian Huang - Department of Statistics, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USAMelinda W. Andreski - Department of Internal Medicine, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USALaura S. Jacobus - University of IowaChristiana M. Taylor - Department of Internal Medicine, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USAGeorge J. Weiner - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Blood, Vol.108(11), pp.2823-2823
- DOI
- 10.1182/blood.V108.11.2823.2823
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 11/16/2006
- Academic Unit
- Holden Comprehensive Cancer Center; Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984363272802771
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