In:
Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2675-2675
Abstract:
Abstract 2675 Poster Board II-651 Interleukin 21 (IL-21) is a novel and highly promising cytokine for the treatment of neoplastic and infectious diseases. Recently, IL-21 has been identified as inducer of plasma cell differentiation. Here we show that CD40 ligand is critically involved in this process and that, in its absence, human B cells differentiate into granzyme B (GzmB)-secreting cytotoxic cells rather than plasma cells. GzmB expression and secretion by human B cells was demonstrated by FACS analysis, ELISpot, ELISA, Sensizyme, Western immunoblotting, RT-PCR, and spinning disk confocal microscopy. GzmB secretion requires the presence of IL-21 and B cell receptor engagement, and depends on phosphorylation of JAK1/3 and STAT3. CD40 ligation effectively suppresses GzmB secretion by B cells, suggesting GrB-secreting B cells play a role in the early phase of inflammatory processes, before CD40 ligand-expressing T cells are present. Of note, ex-vivo re-stimulation of B cells from recently vaccinated individuals with inactivated viruses also induces GzmB expression. GzmB is enzymatically active and GzmB-secreting B cells induce apoptosis in various tumor cell lines, a process we were able to visualize by using spinning disk confocal microscopy. Our data reveal an as yet unrecognized role of IL-21-activated B cells, which involves GzmB secretion and cellular cytotoxicity. Our findings may have implications for the understanding of tumor immunosurveillance and early anti-viral immune responses, and may open novel approaches for the immunotherapy of neoplastic and viral diseases. Disclosures: No relevant conflicts of interest to declare.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood.V114.22.2675.2675
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2009
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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