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Interleukin 21 can induce granzyme B‐secreting cytotoxic B lymphocytes
Author(s) -
Hagn Magdalena,
Sontheimer Kai,
Dahlke Karen,
Beyer Thamara,
Lunov Oleg,
Fabricius Dorit,
Tron Kyrylo,
Nienhaus G. Ulrich,
Simmet Thomas,
Jahrsdörfer Bernd
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb506
Subject(s) - granzyme b , cytotoxic t cell , granzyme , cd40 , immune system , cancer research , biology , microbiology and biotechnology , immunology , cd8 , perforin , biochemistry , in vitro
Interleukin 21 (IL‐21) is a promising cytokine for the treatment of tumors and infections. Recently, IL‐21 was identified as an inducer of plasma cells when combined with CD40 ligand (CD40L). Here we show that in the absence of CD40L B cells (BC) rather differentiate into granzyme B (GzmB)‐secreting cytotoxic cells. GzmB induction in BC requires IL‐21 and BC receptor cross‐linking, and involves phosphorylation of SYK, JAK1/3 and STAT1/3. CD40L effectively suppresses GzmB in BC, suggesting that GzmB‐secreting BC play a role early during inflammation, before CD40L‐expressing T cells are present. This is underlined by our observation that T cell receptor (TCR)‐stimulated, but not fully activated CD4+ T cells express IL‐21 and induce GzmB in co‐cultured BC in an IL‐21 receptor‐dependent manner. BC‐derived GzmB is enzymatically active and induces apoptosis in various tumor cell lines. Our data reveal a novel role of IL‐21‐activated BC, which involves GzmB secretion and 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.