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

Seiji Maruo, Masatsugu Ohora, 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 journalArticle

    56 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

    Fingerprint

    CD40 Ligand
    Viral Tumor Antigens
    Antigen-Presenting Cells
    Interleukin-12
    Cell Communication
    B-Lymphocytes
    T-Lymphocytes
    Cricetulus
    Ovary
    Spleen
    Humoral Immunity
    Cellular Immunity
    Cell Count

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology

    Cite this

    Maruo, S., Ohora, M., Ahn, H. J., Ono, S., Wysocka, M., Kaneko, Y., ... Fujiwara, H. (1997). B Cells Regulate CD40 Ligand-Induced IL-12 Production in Antigen-Presenting Cells (APC) during T Cell/APC Interactions. Journal of Immunology, 158(1), 120-126.

    B Cells Regulate CD40 Ligand-Induced IL-12 Production in Antigen-Presenting Cells (APC) during T Cell/APC Interactions. / Maruo, Seiji; Ohora, Masatsugu; Ahn, Hyun Jong; Ono, Shiro; Wysocka, Maria; Kaneko, Yoriaki; Yagita, Hideo; Okumura, Ko; Kikutani, Hitoshi; Kishimoto, Tadamitsu; Kobayashi, Michiko; Hamaoka, Toshiyuki; Trinchieri, Giorgio; Fujiwara, Hiromi.

    In: Journal of Immunology, Vol. 158, No. 1, 01.01.1997, p. 120-126.

    Research output: Contribution to journalArticle

    Maruo, S, Ohora, M, Ahn, HJ, Ono, S, Wysocka, M, Kaneko, Y, Yagita, H, Okumura, K, Kikutani, H, Kishimoto, T, Kobayashi, M, Hamaoka, T, Trinchieri, G & Fujiwara, H 1997, 'B Cells Regulate CD40 Ligand-Induced IL-12 Production in Antigen-Presenting Cells (APC) during T Cell/APC Interactions', Journal of Immunology, vol. 158, no. 1, pp. 120-126.
    Maruo, Seiji ; Ohora, Masatsugu ; Ahn, Hyun Jong ; Ono, Shiro ; Wysocka, Maria ; Kaneko, Yoriaki ; Yagita, Hideo ; Okumura, Ko ; Kikutani, Hitoshi ; Kishimoto, Tadamitsu ; Kobayashi, Michiko ; Hamaoka, Toshiyuki ; Trinchieri, Giorgio ; Fujiwara, Hiromi. / B Cells Regulate CD40 Ligand-Induced IL-12 Production in Antigen-Presenting Cells (APC) during T Cell/APC Interactions. In: Journal of Immunology. 1997 ; Vol. 158, No. 1. pp. 120-126.
    @article{18118b8e1dad4361b305381885d55ca1,
    title = "B Cells Regulate CD40 Ligand-Induced IL-12 Production in Antigen-Presenting Cells (APC) during T Cell/APC Interactions",
    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.",
    author = "Seiji Maruo and Masatsugu Ohora and Ahn, {Hyun Jong} and Shiro Ono and Maria Wysocka and Yoriaki Kaneko and Hideo Yagita and Ko Okumura and Hitoshi Kikutani and Tadamitsu Kishimoto and Michiko Kobayashi and Toshiyuki Hamaoka and Giorgio Trinchieri and Hiromi Fujiwara",
    year = "1997",
    month = "1",
    day = "1",
    language = "English",
    volume = "158",
    pages = "120--126",
    journal = "Journal of Immunology",
    issn = "0022-1767",
    publisher = "American Association of Immunologists",
    number = "1",

    }

    TY - JOUR

    T1 - B Cells Regulate CD40 Ligand-Induced IL-12 Production in Antigen-Presenting Cells (APC) during T Cell/APC Interactions

    AU - Maruo, Seiji

    AU - Ohora, Masatsugu

    AU - Ahn, Hyun Jong

    AU - Ono, Shiro

    AU - Wysocka, Maria

    AU - Kaneko, Yoriaki

    AU - Yagita, Hideo

    AU - Okumura, Ko

    AU - Kikutani, Hitoshi

    AU - Kishimoto, Tadamitsu

    AU - Kobayashi, Michiko

    AU - Hamaoka, Toshiyuki

    AU - Trinchieri, Giorgio

    AU - Fujiwara, Hiromi

    PY - 1997/1/1

    Y1 - 1997/1/1

    N2 - 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.

    AB - 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.

    UR - http://www.scopus.com/inward/record.url?scp=0030639614&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=0030639614&partnerID=8YFLogxK

    M3 - Article

    C2 - 8977182

    AN - SCOPUS:0030639614

    VL - 158

    SP - 120

    EP - 126

    JO - Journal of Immunology

    JF - Journal of Immunology

    SN - 0022-1767

    IS - 1

    ER -