ArticleThe Journal of experimental medicine2022
Bhlhe40 function in activated B and TFH cells restrains the GC reaction and prevents lymphomagenesis.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 36 citations in OpenAlex.
- RNA binding protein Sam68 promotes germinal center reaction and IgG response through regulation of miR29.Cellular and molecular life sciences : CMLS · 2026Article
- Optimal CXCR5 expression during Tfh maturation involves the Bhlhe40-Pou2af1 axis.Cell reports · 2025Article
- ST2Clinical and translational allergy · 2025Article
- The impact of NF-κB2 mutations on Tfh cell differentiation and their critical role in immune function.Translational pediatrics · 2025Article
- Signaling Activation and Modulation in Extrafollicular B Cell Responses.Immunological reviews · 2025Review
- Signaling Activation and Modulation in Extrafollicular B Cell Responses.Immunological reviews · 2025Review
- Article
- Direct presentation of inflammation-associated self-antigens by thymic innate-like T cells induces elimination of autoreactive CD8Nature immunology · 2024Article
- Bhlhe40 Regulates Proliferation and Angiogenesis in Mouse Embryoid Bodies under Hypoxia.International journal of molecular sciences · 2024Article
- Bhlhe40 Promotes CD4+ T Helper 1 Cell and Suppresses T Follicular Helper Cell Differentiation during Viral Infection.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Type I interferons induce an epigenetically distinct memory B cell subset in chronic viral infection.Immunity · 2024Article
- The genetic regulatory architecture and epigenomic basis for age-related changes in rattlesnake venom.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Help me help you: emerging concepts in T follicular helper cell differentiation, identity, and function.Current opinion in immunology · 2024Review
- Defective mitochondria remodelling in B cells leads to an aged immune response.Nature communications · 2024Article
- Follicular lymphoma B cells exhibit heterogeneous transcriptional states with associated somatic alterations and tumor microenvironments.Cell reports. Medicine · 2024Article
- Bob1 maintains T follicular helper cells for long-term humoral immunity.Communications biology · 2024Article
- Article
- BHLHE40 drives protective polyfunctional CD4 T cell differentiation in the female reproductive tract against Chlamydia.PLoS pathogens · 2024Article
- T Cell Subsets and Immune Homeostasis.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Bhlhe40 limits early IL-10 production from CD4Infection and immunity · 2023Article
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Authors and funding
11 authors at 5 institutions in 4 countries.
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Abstract
The generation of high-affinity antibodies against pathogens and vaccines requires the germinal center (GC) reaction, which relies on a complex interplay between specialized effector B and CD4 T lymphocytes, the GC B cells and T follicular helper (TFH) cells. Intriguingly, several positive key regulators of the GC reaction are common for both cell types. Here, we report that the transcription factor Bhlhe40 is a crucial cell-intrinsic negative regulator affecting both the B and T cell sides of the GC reaction. In activated CD4 T cells, Bhlhe40 was required to restrain proliferation, thus limiting the number of TFH cells. In B cells, Bhlhe40 executed its function in the first days after immunization by selectively restricting the generation of the earliest GC B cells but not of early memory B cells or plasmablasts. Bhlhe40-deficient mice with progressing age succumbed to a B cell lymphoma characterized by the accumulation of monoclonal GC B-like cells and polyclonal TFH cells in various tissues.
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