IL-21-induced Bε cell apoptosis mediated by natural killer T cells suppresses IgE responses

Michishige Harada, Kumiko Magara-Koyanagi, Hiroshi Watarai, Yuko Nagata, Yasuyuki Ishii, Satoshi Kojo, Shigetoshi Horiguchi, Yoshitaka Okamoto, Toshinori Nakayama, Nobutaka Suzuki, Wen Chen Yeh, Shizuo Akira, Hiroshi Kitamura, Osamu Ohara, Ken Ichiro Seino, Masaru Taniguchi

Research output: Contribution to journalArticlepeer-review

102 Citations (Scopus)


Epidemiological studies have suggested that the recent increase in the incidence and severity of immunoglobulin (Ig)E-mediated allergic disorders is inversely correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination; however, the underlying mechanisms remain uncertain. Here, we demonstrate that natural killer T (NKT) cells in mice and humans play a crucial role in the BCG-induced suppression of IgE responses. BCG-activated murine Vα14 NKT cells, but not conventional CD4 T cells, selectively express high levels of interleukin (IL)-21, which preferentially induces apoptosis in Bε cells. Signaling from the IL-21 receptor increases the formation of a complex between Bcl-2 and the proapoptotic molecule Bcl-2-modifying factor, resulting in Bε cell apoptosis. Similarly, BCG vaccination induces IL-21 expression by human peripheral blood mononuclear cells (PBMCs) in a partially NKT cell-dependent fashion. BCG-activated PBMCs significantly reduce IgE production by human B cells. These findings provide new insight into the therapeutic effect of BCG in allergic diseases. JEM

Original languageEnglish
Pages (from-to)2929-2937
Number of pages9
JournalJournal of Experimental Medicine
Issue number13
Publication statusPublished - Dec 25 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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