B-chronic lymphocytic leukemia cells and other B cells can produce granzyme B and gain cytotoxic potential after interleukin-21-based activation.
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.
Jahrsdörfer
Bernd
B
Holden Cancer Center at the University of Iowa, 5970Z JPP, University of Iowa, Iowa City, IA 52242, USA.
Blackwell
Sue E
SE
Wooldridge
James E
JE
Huang
Jian
J
Andreski
Melinda W
MW
Jacobus
Laura S
LS
Taylor
Christiana M
CM
Weiner
George J
GJ
D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D002478:Cells, Cultured; D053804:Granzymes; D006801:Humans; D066298:In Vitro Techniques; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000235:genetics; D053655:Receptors, Interleukin-21; D011994:Recombinant Proteins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D000098546:Interleukin-21
C408982:CPG-oligonucleotide; C508117:IL21R protein, human; D053738:Interleukin-21 Receptor alpha Subunit; D007378:Interleukins; D052118:Lysosomal-Associated Membrane Protein 1; D009838:Oligodeoxyribonucleotides; D018123:Receptors, Interleukin; D053655:Receptors, Interleukin-21; D011994:Recombinant Proteins; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; D000098546:Interleukin-21