In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitment

Deniz Durali, Marie Ghislaine De Goër De Herve, Julien Giron-Michel, Bruno Azzarone, Jean François Delfraissy, Yassine Taoufik

Research output: Contribution to journalArticle

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Abstract

Two functionally distinct subsets of B cells that produce Th1- and Th2-like patterns of cytokines have recently been identified. Interleukin-12 (IL-12) is a critical immunoregulatory cytokine that promotes Th1 differentiation through activation of signal transducer and activator of transcription 4 (STAT4). IL-12 has been reported to induce interferon γ (IFN-γ) production in B cells, but the relevant signaling pathways are poorly documented. Here, in human primary B cells, we found a functional IL-12 receptor (IL-12R) that internalizes following IL-12 binding. IFN-γ and, to a lesser extent, IL-12 positively regulated the IL-12Rβ2 subunit but had no effect on IL-12Rβ1. On examining the effect of IL-12 on STAT4 and T-bet (2 key factors involved in IFN-β promoter activation), we found that IL-12 induced the phosphorylation and nuclear translocation of STAT4. IL-12-dependent constitutive STAT4 activation was also observed in the Epstein-Barr virus (EBV)-transformed B-cell line RPMI 8866 that spontaneously produces IL-12. T-bet expression has been shown to be dependent on STAT1. IL-12 had no direct effect on STAT1 activation or T-bet expression in primary B cells. In contrast, IL-12-induced IFN-γ led to STAT1 activation, strong expression of T-bet, and IFN-γ expression. IL-12 therefore initiates a cascade of events in B cells, including STAT4 activation, IL-12Rβ2 up-regulation, IFN-γ production, and T-bet up-regulation, potentially leading to Th1-like differentiation.

Original languageEnglish
Pages (from-to)4084-4089
Number of pages6
JournalBlood
Volume102
Issue number12
DOIs
Publication statusPublished - Dec 1 2003

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Interleukin-12
B-Lymphocytes
STAT4 Transcription Factor
Cells
Interferons
Chemical activation
Transcriptional Activation
Up-Regulation
Interleukin-12 Receptors
Cytokines
B-Lymphocyte Subsets
Transformed Cell Line
Phosphorylation
Human Herpesvirus 4
Viruses

ASJC Scopus subject areas

  • Hematology

Cite this

Durali, D., De Goër De Herve, M. G., Giron-Michel, J., Azzarone, B., Delfraissy, J. F., & Taoufik, Y. (2003). In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitment. Blood, 102(12), 4084-4089. https://doi.org/10.1182/blood-2003-02-0518

In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitment. / Durali, Deniz; De Goër De Herve, Marie Ghislaine; Giron-Michel, Julien; Azzarone, Bruno; Delfraissy, Jean François; Taoufik, Yassine.

In: Blood, Vol. 102, No. 12, 01.12.2003, p. 4084-4089.

Research output: Contribution to journalArticle

Durali, D, De Goër De Herve, MG, Giron-Michel, J, Azzarone, B, Delfraissy, JF & Taoufik, Y 2003, 'In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitment', Blood, vol. 102, no. 12, pp. 4084-4089. https://doi.org/10.1182/blood-2003-02-0518
Durali D, De Goër De Herve MG, Giron-Michel J, Azzarone B, Delfraissy JF, Taoufik Y. In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitment. Blood. 2003 Dec 1;102(12):4084-4089. https://doi.org/10.1182/blood-2003-02-0518
Durali, Deniz ; De Goër De Herve, Marie Ghislaine ; Giron-Michel, Julien ; Azzarone, Bruno ; Delfraissy, Jean François ; Taoufik, Yassine. / In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitment. In: Blood. 2003 ; Vol. 102, No. 12. pp. 4084-4089.
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