ArticleImmunology and cell biology2017
IL4 and IL21 cooperate to induce the high Bcl6 protein level required for germinal center formation.
Article in Immunology and cell biology, 2017. 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, 52 citations in OpenAlex.
- Epigenetic signatures mark early peripheral human B lineage bifurcation and differential transcriptional profiles in mature populations.Nature communications · 2026Article
- Mixed Signals: T Cells as Architects of IgE Immunity.Immunological reviews · 2026Review
- STAT6: Multidimensional analysis from hematopoietic immune regulation to pathogenesis mechanisms and therapeutic targets in hematologic malignancies.Annals of hematology · 2026Review
- T follicular helper cell development during malaria.Current opinion in immunology · 2025Review
- Polarization of the memory B-cell response.Journal of leukocyte biology · 2025Review
- Tumor Biology Hides Novel Therapeutic Approaches to Diffuse Large B-Cell Lymphoma: A Narrative Review.International journal of molecular sciences · 2024Review
- Immature B cell homing shapes human lymphoid tissue structure and function.The Journal of experimental medicine · 2024Article
- Interleukin-4 downregulates transcription factor BCL6 to promote memory B cell selection in germinal centers.Immunity · 2024Article
- Article
- Interferon-γ production by Tfh cells is required for CXCR3Immunity · 2023Article
- Clinical prognostic value of OSGIN2 in gastric cancer and its proliferative effect in vitro.Scientific reports · 2023Article
- NF-kB's contribution to B cell fate decisions.Frontiers in immunology · 2023Review
- miRNA Expression May Have Implications for Immunotherapy in PDGFRA Mutant GISTs.International journal of molecular sciences · 2022Article
- Diverging regulation of Bach2 protein and RNA expression determine cell fate in early B cell response.Cell reports · 2022Article
- Temporally Evolving and Context-Dependent Functions of Cytokines That Regulate Murine Anti-Pathogens (Basel, Switzerland) · 2022Review
- Patient-Specific Modeling of Diffuse Large B-Cell Lymphoma.Biomedicines · 2021Article
- Follicular dendritic cells restrict interleukin-4 availability in germinal centers and foster memory B cell generation.Immunity · 2021Article
- Transcriptional regulation of memory B cell differentiation.Nature reviews. Immunology · 2021Review
- The Imbalance of Circulating Follicular T Helper Cell Subsets in Primary Sjögren's Syndrome Associates With Serological Alterations and Abnormal B-Cell Distribution.Frontiers in immunology · 2021Article
- The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development.Nature immunology · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bcl6 (B-cell lymphoma 6) is a transcriptional repressor and critical mediator of the germinal center reaction during a T-cell-dependent antibody response, where it enables somatic hypermutation of immunoglobulin genes and inhibits terminal differentiation via repression of Blimp1. It can also contribute to the development of diffuse large B-cell lymphoma when expressed inappropriately. Bcl6 regulation is mediated both at the transcriptional and post-transcriptional levels, and in particular a strong signal through the B-cell receptor causes rapid proteasomal degradation of Bcl6. Despite the importance of Bcl6 in both immunity and cancer, little is known about how other extrinsic factors regulate Bcl6 in B cells. Here we show that Bcl6 is indeed highly unstable in B cells after a B-cell receptor (BCR) signal, but that the T-cell-derived cytokines interleukin 4 (IL4) and IL21 counteract BCR-mediated degradation, preserving Bcl6 protein levels. Stat6, downstream of IL4, can induce Bcl6 transcription directly. In vivo, B-cell intrinsic loss of IL4 or IL21 signaling reduces the magnitude or duration of the GC response, respectively, while their combined loss almost completely eliminates the GC response. This work provides key insights into the effect mediated by T-follicular helper cytokines on Bcl6 regulation.
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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.