期刊
IMMUNOLOGY AND CELL BIOLOGY
卷 90, 期 4, 页码 457-467出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/icb.2011.64
关键词
B cell; IL-21; CD40 ligand; neoplasm; tumor; virus
资金
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [JA 1769/2-2]
- Deutsche Jose Carreras Leukamiestiftung [SP 07/10]
- Deutscher Akademischer Austauschdienst (DAAD, German Academic Exchange Service) [D/08/11870]
Recently, CD4(+) T helper cells were shown to induce differentiation of human B cells into plasma cells by expressing interleukin (IL-)21 and CD40 ligand (CD40L). In the present study we show, that in the absence of CD40L, CD4(+) T cell-derived IL-21 induces differentiation of B cells into granzyme B (GzmB)-secreting cytotoxic cells. Using fluorescence-activated cell sorting (FACS) analysis, ELISpot and confocal microscopy, we demonstrate that CD4(+) T cells, activated via their T-cell receptor without co-stimulation, can produce IL-21, but do not express CD40L and rapidly induce GzmB in co-cultured B cells in an IL-21 receptor-dependent manner. Of note, we confirmed these results with recombinant reagents, highlighting that CD40L suppresses IL-21-induced GzmB induction in B cells in a dose-dependent manner. Surprisingly, although GzmB-secreting B cells did not express perforin, they were able to transfer active GzmB to tumor cell lines, thereby effectively inducing apoptosis. In contrast, no cytotoxic effects were found when effector B cells were activated with IL-2 instead of IL-21 or when target cells were cultured with IL-21 alone. Our findings suggest GzmB(+) cytotoxic B cells may have a role in early cellular immune responses including tumor immunosurveillance, before fully activated, antigen-specific cytotoxic T cells are on the spot. CD40 ligand determines whether IL-21 induces differentiation of B cells into plasma cells or into granzyme B-secreting cytotoxic cells. Immunology and Cell Biology (2012) 90, 457-467; doi:10.1038/icb.2011.64; published online 2 August 2011
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