ArticleEMBO reports2015
LKB1 inhibition of NF-κB in B cells prevents T follicular helper cell differentiation and germinal center formation.
Article in EMBO reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Regulatory Effect of Iguratimod on the Balance of Th Subsets and Inhibition of Inflammatory Cytokines in Patients with Rheumatoid Arthritis.Mediators of inflammation · 2015Trial
- A quinazoline derivative suppresses B cell hyper-activation and ameliorates the severity of systemic lupus erythematosus in mice.Frontiers in pharmacology · 2023Article
- Loss of LKB1-NUAK1 signalling enhances NF-κB activity in a spheroid model of high-grade serous ovarian cancer.Scientific reports · 2022Article
- Integrated bioinformatics and network pharmacology to identify the therapeutic target and molecular mechanisms of Huangqin decoction on ulcerative Colitis.Scientific reports · 2022Article
- Liver kinase B1 rs9282860 polymorphism and risk for multiple sclerosis in White and Black Americans.Multiple sclerosis and related disorders · 2021Article
- Cyclic Helix B Peptide Prolongs Skin Allograft SurvivalFrontiers in immunology · 2021Article
- AMPK Metabolism in the B Lineage Modulates Humoral Responses.Immunometabolism · 2021Article
- Liver kinase B1 depletion from astrocytes worsens disease in a mouse model of multiple sclerosis.Glia · 2020Article
- Ampk regulates IgD expression but not energy stress with B cell activation.Scientific reports · 2019Article
- Mycobacterium tuberculosis Mannose-Capped Lipoarabinomannan Induces IL-10-Producing B Cells and Hinders CD4iScience · 2019Article
- Lose appetite, lose control: integrins and noncanonical autophagy regulate germinal center reactions.The Journal of clinical investigation · 2018Article
- Lkb1 deletion in murine B lymphocytes promotes cell death and cancer.Experimental hematology · 2017Article
- Emerging Roles for Noncanonical NF-κB Signaling in the Modulation of Inflammatory Bowel Disease Pathobiology.Inflammatory bowel diseases · 2016Review
- Abnormalities of plasma cytokines and spleen in senile APP/PS1/Tau transgenic mouse model.Scientific reports · 2015Article
- LKB1 regulates germinal center formation and termination.Cell cycle (Georgetown, Tex.) · 2015Article
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
T-cell-dependent antigenic stimulation drives the differentiation of B cells into antibody-secreting plasma cells and memory B cells, but how B cells regulate this process is unclear. We show that LKB1 expression in B cells maintains B-cell quiescence and prevents the premature formation of germinal centers (GCs). Lkb1-deficient B cells (BKO) undergo spontaneous B-cell activation and secretion of multiple inflammatory cytokines, which leads to splenomegaly caused by an unexpected expansion of T cells. Within this cytokine response, increased IL-6 production results from heightened activation of NF-κB, which is suppressed by active LKB1. Secreted IL-6 drives T-cell activation and IL-21 production, promoting T follicular helper (TFH ) cell differentiation and expansion to support a ~100-fold increase in steady-state GC B cells. Blockade of IL-6 secretion by BKO B cells inhibits IL-21 expression, a known inducer of TFH -cell differentiation and expansion. Together, these data reveal cell intrinsic and surprising cell extrinsic roles for LKB1 in B cells that control TFH -cell differentiation and GC formation, and place LKB1 as a central regulator of T-cell-dependent humoral immunity.
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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.