B Cells Regulate CD40 Ligand-Induced IL-12 Production in Antigen-Presenting Cells (APC) during T Cell/APC Interactions

Seiji Maruo, Masatsugu Oh-Hora, Hyun Jong Ahn, Shiro Ono, Maria Wysocka, Yoriaki Kaneko, Hideo Yagita, Ko Okumura, Hitoshi Kikutani, Tadamitsu Kishimoto, Michiko Kobayashi, Toshiyuki Hamaoka, Giorgio Trinchieri, Hiromi Fujiwara

    Research output: Contribution to journalArticlepeer-review

    57 Citations (Scopus)

    Abstract

    Although stimulation of freshly isolated murine spleen cells with anti-CD3 mAb or Con A failed to generate IL-12 production, the same cell preparations depleted of B cells produced IL-12. Addition of normal B cells inhibited IL-12 production in a cell number-dependent manner. IL-12 production was dependent on the presence of CD4+, but not of CD8+, T cells, and inhibited by addition of anti-CD40 ligand (CD40L) mAb. Anti-CD3 or Con A stimulation induced CD40L expression only on CD4+ T cells, which was inhibited in the presence of B cells. IL-12 production was also induced by interactions between CD40L-transfected Chinese hamster ovary cells and splenocytes depleted of T and B cells, but not of APC, indicating CD40L-induced IL-12 production by APC. The involvement of CD40 molecules was examined by comparing the ability of cells from CD40-deficient (CD40 -/-) and wild-type mice (CD40 +/+) to produce IL-12. Spleen cells from CD40 -/- and CD40 +/+ mice produced comparable amounts of IL-12 in response to bacterial stimuli. However, the B cell-depleted fraction from CD40 -/- mice failed to produce IL-12 when stimulated with anti-CD3 or Con A or when cocultured with CD40L-expressing Chinese hamster ovary cells. These results indicate that CD40L expressed on activated T cells induces APC to produce IL-12 through CD40/CD40L interaction, but this pathway is competitively inhibited by CD40+ B cells incapable of producing IL-12 upon stimulation with CD40L. Thus, this might represent a novel mechanism underlying the regulation of cell-mediated and humoral immunity.

    Original languageEnglish
    Pages (from-to)120-126
    Number of pages7
    JournalJournal of Immunology
    Volume158
    Issue number1
    Publication statusPublished - Jan 1 1997

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

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