ArticleThe Journal of experimental medicine2023
IL-21 shapes germinal center polarization via light zone B cell selection and cyclin D3 upregulation.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Therapeutic Immune Reprogramming by Rapamycin Attenuates Plaque Inflammation and Lymphoid Immune Responses in Aged Atherosclerotic Mice.Aging cell · 2026Article
- Targeting T follicular helper cells for lifelong health.Nature reviews. Drug discovery · 2026Review
- An "old" cytokine's new trick: IL-1β in B cells and the germinal center.Function (Oxford, England) · 2026Review
- Article
- Mastering Immunity: Antibody Feedback as a Driver of Germinal Center Fate and Vaccine Responses.European journal of immunology · 2025Review
- Germinal Center B cells provide essential IL-1β signals to TFH cells via canonical NLRP3 inflammasome activity post influenza infection.PLoS pathogens · 2025Article
- KMT2D coordinates antiviral CD4Cell reports · 2025Article
- Emerging Concepts in Cytokine Regulation of Airway Remodeling in Asthma.Immunological reviews · 2025Review
- IL-21 shapes the B cell response in a context-dependent manner.Cell reports · 2025Article
- T follicular helper cell is essential for M2 macrophage polarization and pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension.Respiratory research · 2024Article
- IL-2 family cytokines IL-9 and IL-21 differentially regulate innate and adaptive type 2 immunity in asthma.The Journal of allergy and clinical immunology · 2024Article
- CD4 T Cell-Derived IL-21 Is Critical for Sustaining Plasmodium Infection-Induced Germinal Center Responses and Promoting the Selection of Memory B Cells with Recall Potential.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Help me help you: emerging concepts in T follicular helper cell differentiation, identity, and function.Current opinion in immunology · 2024Review
- T-cell help in the germinal center: homing in on the role of IL-21.International immunology · 2024Article
- Interleukin 9 mediates T follicular helper cell activation to promote antibody responses.Frontiers in immunology · 2024Article
- Accumulation of immune-suppressive CD4 + T cells in aging - tempering inflammaging at the expense of immunity.Seminars in immunology · 2023Review
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Germinal center (GC) dysregulation has been widely reported in the context of autoimmunity. Here, we show that interleukin 21 (IL-21), the archetypal follicular helper T cell (Tfh) cytokine, shapes the scale and polarization of spontaneous chronic autoimmune as well as transient immunization-induced GC. We find that IL-21 receptor deficiency results in smaller GC that are profoundly skewed toward a light zone GC B cell phenotype and that IL-21 plays a key role in selection of light zone GC B cells for entry to the dark zone. Light zone skewing has been previously reported in mice lacking the cell cycle regulator cyclin D3. We demonstrate that IL-21 triggers cyclin D3 upregulation in GC B cells, thereby tuning dark zone inertial cell cycling. Lastly, we identify Foxo1 regulation as a link between IL-21 signaling and GC dark zone formation. These findings reveal new biological roles for IL-21 within GC and have implications for autoimmune settings where IL-21 is overproduced.
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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.