ArticleThe Journal of experimental medicine1999
Human non-germinal center B cell interleukin (IL)-12 production is primarily regulated by T cell signals CD40 ligand, interferon gamma, and IL-10: role of B cells in the maintenance of T cell responses.
Article in The Journal of experimental medicine, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 134 citations in OpenAlex.
- Coordinated Regulation of Extrafollicular B Cell Responses by IL-12 and IFNγ.Immunological reviews · 2025Review
- Article
- Longitudinal liver sampling in patients with chronic hepatitis B starting antiviral therapy reveals hepatotoxic CD8+ T cells.The Journal of clinical investigation · 2023Article
- Comprehensive overview of COVID-19-related respiratory failure: focus on cellular interactions.Cellular & molecular biology letters · 2022Review
- B cell-derived IL-27 promotes control of persistent LCMV infection.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- T cell transgressions: Tales of T cell form and function in diverse disease states.International reviews of immunology · 2022Review
- Article
- Role of Viral and Host microRNAs in Immune Regulation of Epstein-Barr Virus-Associated Diseases.Frontiers in immunology · 2020Review
- Glucocorticoid-Induced Leucine Zipper Inhibits Interferon-Gamma Production in B Cells and Suppresses Colitis in Mice.Frontiers in immunology · 2018Article
- B cell-derived IL-4 acts on podocytes to induce proteinuria and foot process effacement.JCI insight · 2017Article
- B-cells with a FasL expressing regulatory phenotype are induced following successful anti-tuberculosis treatment.Immunity, inflammation and disease · 2017Article
- Article
- Distinct TLR-mediated cytokine production and immunoglobulin secretion in human newborn naïve B cells.Innate immunity · 2016Article
- The role of B cells and humoral immunity in Mycobacterium tuberculosis infection.Seminars in immunology · 2014Review
- B cells promote induction of experimental autoimmune encephalomyelitis by facilitating reactivation of T cells in the central nervous system.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Prevention of adverse events of interferon γ gene therapy by gene delivery of interferon γ-heparin-binding domain fusion protein in mice.Molecular therapy. Methods & clinical development · 2014Article
- B cell-regulated immune responses in tumor models and cancer patients.Oncoimmunology · 2013Review
- The role of B cells and humoral immunity in Mycobacterium tuberculosis infection.Advances in experimental medicine and biology · 2013Review
- Bispecific and trispecific killer cell engagers directly activate human NK cells through CD16 signaling and induce cytotoxicity and cytokine production.Molecular cancer therapeutics · 2012Article
- TLR1/2, TLR7, and TLR9 signals directly activate human peripheral blood naive and memory B cell subsets to produce cytokines, chemokines, and hematopoietic growth factors.Journal of clinical immunology · 2011Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Interleukin (IL)-12 is expressed mainly in antigen-presenting cells after challenge with microbial material or after CD40 activation. Although IL-12 was cloned from human Epstein-Barr virus (EBV)-transformed B cell lines, surprisingly, CD40 ligation on murine B cells did not lead to IL-12 production, suggesting that murine B cells do not produce IL-12. Here we demonstrate that a subset of human tonsillar B cells can be induced to express and secrete bioactive IL-12. The major stimulus to produce IL-12 in human B cells was CD40 ligation. In contrast, B cell receptor cross-linking did not induce IL-12. Expression of IL-12 after CD40 activation was restricted to CD38(-)IgD+/- non-germinal center (non-GC) B cells. CD40 ligation and interferon (IFN)-gamma exhibited synergistic effects on IL-12 production, whereas IL-10 abrogated and IL-4 significantly inhibited IL-12 production by these B cells. In contrast to IL-12, production of IL-6 is conversely regulated, leading to significant increase after CD40 ligation in the presence of the T helper type 2 (Th2) cytokine IL-4. Cord blood T cells skewed towards either a Th1 or a Th2 phenotype maintained their cytokine expression pattern when restimulated with allogeneic resting B cells. Blockade of CD40 and/or IL-12 during T-B interaction significantly reduced IFN-gamma production by the T cells. This suggests a model whereby B cells produce either IL-12 or IL-6 after contact with T cells previously differentiated towards Th1 or Th2. Furthermore, IL-12 and IL-6 might provide a positive feedback during cognate T-B interactions, thereby maintaining T cells' differentiation pattern during amplification of the immune response.
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