In:
Immunology & Cell Biology, Wiley, Vol. 90, No. 4 ( 2012-04), p. 457-467
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0818-9641
,
1440-1711
Language:
English
Publisher:
Wiley
Publication Date:
2012
detail.hit.zdb_id:
2011707-3
SSG:
12
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