Abstract
Interleukin 21-Based Therapy Can Induce Human B Cells To Produce Granzyme B and Express Other Features of Cytotoxic Lymphocytes
Blood, Vol.108(11), pp.3886-3886
11/16/2006
DOI: 10.1182/blood.V108.11.3886.3886
Abstract
Abstract
B cells are not currently known to be capable of producing granzyme B or being cytotoxic. We recently found that human B cells activated with Interleukin 21 (IL-21) and antibodies to the B cell receptor (BCR) or immunostimulatory oligonucleotides (CpG ODN), can produce granzyme B. Further studies were done to assess the biological and potential therapeutic significance of this finding. Granzyme B ELISpot, intracellular staining for granzyme-B, quantitative real time RT-PCR for granzyme B messenger RNA and gene expression array confirmed B cells obtained from the peripheral blood of normal individuals (Fig. 1) and many B cell lines including Namalwa, Daudi, Ramos and EBV-transformed lymphoblasts, can be induced to produce granzyme B. This granzyme B is functional as demonstrated by cleavage of a granzyme B-sensitive colorimetric substrate. IL-21 based treatment also increased the transcription of the gene for perforin and the production of Interferon-γ in select B cell populations. We conclude that IL-21 based therapy can induce B cells to produce functional granzyme B and other components known to be present in the cytotoxic granules of CTL and NK cells. These unexpected findings could have significant implications on our understanding of the role of B cells in immune regulation and for a variety of immune phenomena including auto-, cancer and infectious immunity.
Figure 1. Interleukin 21 (IL-21) induces de-novo synthesis of Granzyme B by activated B cells. Peripheral blood mononuclear cells (PBMC) were stimulated with the above depicted agents for 18 hours. After further incubtion with Brefeldin A for 4 hours cells were harvested, fixed, permeabilized, stained with PE- and PE-Cy5-labeled antibodies against Granzyme B and CD19, and analyzed flowcytometrically. Figure 1. Interleukin 21 (IL-21) induces de-novo synthesis of Granzyme B by activated B cells. Peripheral blood mononuclear cells (PBMC) were stimulated with the above depicted agents for 18 hours. After further incubtion with Brefeldin A for 4 hours cells were harvested, fixed, permeabilized, stained with PE- and PE-Cy5-labeled antibodies against Granzyme B and CD19, and analyzed flowcytometrically.
Details
- Title: Subtitle
- Interleukin 21-Based Therapy Can Induce Human B Cells To Produce Granzyme B and Express Other Features of Cytotoxic Lymphocytes
- Creators
- Bernd Jahrsdoerfer - University of IowaSue M. Blackwell - 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.3886-3886
- DOI
- 10.1182/blood.V108.11.3886.3886
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 11/16/2006
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984363424202771
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