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Human B cells differentiate into granzyme B‐secreting cytotoxic B lymphocytes upon incomplete T‐cell help
Author(s) -
Hagn Magdalena,
Sontheimer Kai,
Dahlke Karen,
Brueggemann Sabine,
Kaltenmeier Christof,
Beyer Thamara,
Hofmann Stefanie,
Lunov Oleg,
Barth Thomas FE,
Fabricius Dorit,
Tron Kyrylo,
Nienhaus Gerd Ulrich,
Simmet Thomas,
Schrezenmeier Hubert,
Jahrsdörfer Bernd
Publication year - 2012
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2011.64
Subject(s) - cytotoxic t cell , granzyme b , cd40 , interleukin 21 , granzyme , microbiology and biotechnology , interleukin 12 , antigen presenting cell , perforin , biology , b 1 cell , chemistry , in vitro , biochemistry
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.