ArticleInternational immunology2009
IL-6 produced by immune complex-activated follicular dendritic cells promotes germinal center reactions, IgG responses and somatic hypermutation.
Article in International immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 88 citations in OpenAlex.
- An "old" cytokine's new trick: IL-1β in B cells and the germinal center.Function (Oxford, England) · 2026Review
- Serial intravital microscopy reveals temporal dynamics of autoreactive germinal centers in the spleen.iScience · 2026Article
- Diversity and Epitope Spreading of Anti-RNA Polymerase III Antibodies in Systemic Sclerosis: A Potential Biomarker for Skin and Lung Involvement.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
- Unique and redundant roles of mouse BCMA, TACI, BAFF, APRIL, and IL-6 in supporting antibody-producing cells in different tissues.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Examining B-cell dynamics and responsiveness in different inflammatory milieus using an agent-based model.PLoS computational biology · 2024Article
- The advent of immune stimulating CAFs in cancer.Nature reviews. Cancer · 2023Review
- C-type lectin receptor agonists elicit functional IL21-expressing Tfh cells and induce primary B cell responses in neonates.Frontiers in immunology · 2023Article
- Follicular dendritic cell differentiation is associated with distinct synovial pathotype signatures in rheumatoid arthritis.Frontiers in medicine · 2022Article
- Compartmentalized multicellular crosstalk in lymph nodes coordinates the generation of potent cellular and humoral immune responses.European journal of immunology · 2021Review
- Fibroblasts as immune regulators in infection, inflammation and cancer.Nature reviews. Immunology · 2021Review
- IL-6 signaling mediates the germinal center response, IgM production and nociceptive sensitization in male mice after tibia fracture.Brain, behavior, and immunity · 2021Article
- Transcription tipping points for T follicular helper cell and T-helper 1 cell fate commitment.Cellular & molecular immunology · 2021Review
- Lymphoid stromal cells-more than just a highway to humoral immunity.Oxford open immunology · 2021Review
- Lymph Node Stromal Cells: Diverse Meshwork Structures Weave Functionally Subdivided Niches.Current topics in microbiology and immunology · 2021Article
- Lymph node stromal cells: cartographers of the immune system.Nature immunology · 2020Review
- Mucosal T follicular helper cells in SIV-infected rhesus macaques: contributing role of IL-27.Mucosal immunology · 2019Article
- Toll-Like Receptor 7 Enhances Rabies Virus-Induced Humoral Immunity by Facilitating the Formation of Germinal Centers.Frontiers in immunology · 2019Article
- Identification of a new subset of lymph node stromal cells involved in regulating plasma cell homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Altered immune cell follicular dynamics in HIV infection following influenza vaccination.The Journal of clinical investigation · 2018Article
- Interleukin-6: designing specific therapeutics for a complex cytokine.Nature reviews. Drug discovery · 2018Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Reports that follicular dendritic cells (FDCs) produce IL-6 prompted the hypotheses that immune complexes (ICs) induce FDCs to produce IL-6 and that FDC-IL-6 promotes germinal center (GC) reactions, somatic hypermutation (SHM) and IgG production. FDCs were activated in vitro by addition of ICs and FDC-IL-6 production was determined. Wild-type (WT) and IL-6 knockout (KO) mice, as well as chimeras with WT and IL-6 KO cells, were immunized with (4-hydroxy-3-nitrophenyl)-acetyl (NP)-chicken gamma globulin (CGG) and used to study anti-(4-hydroxy-3-iodo-5-nitrophenyl) acetyl (NIP) responses, GC formation and SHM in the VH186.2 gene segment in Ig-gamma. FDC-IL-6 increased when FDCs encountered ICs. At low immunogen dose, 1 microg NP-CGG per mouse, the IgG anti-NIP response in IL-6 KO mice was low and immunohistochemistry revealed a reduction in both the number and size of GCs. The physiological relevance of FDC-IL-6 was apparent in the chimeric mice where total splenocytes from WT mice were unable to provide the IL-6 needed for normal IgG and GC responses in IL-6 KO animals with IL-6-defective FDCs. Moreover, the rate of mutation decreased from 18 to 8.9 mutations per 1000 bases (P < 0.001) in WT versus IL-6 KO mice. Addition of anti-IL-6 to GC reactions in vitro reduced antibody levels and SHM from 3.5 to 0.65 mutations per 1000 bases (P < 0.02). Thus, the absence of FDC-IL-6 correlated with a reduction in SHM that coincided with the reduction in GCs and specific anti-NIP. This is the first study to document that ICs induce FDC-IL-6 and that FDC-derived IL-6 is physiologically relevant in generating optimal GC reactions, SHM and IgG levels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.