ArticleJournal of immunology (Baltimore, Md. : 1950)2008
ICOS, CD40, and lymphotoxin beta receptors signal sequentially and interdependently to initiate a germinal center reaction.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 43 citations in OpenAlex.
- Lymphotoxin-dependent elevated meningeal CXCL13:BAFF ratios drive gray matter injury.Nature immunology · 2026Article
- Spatial profiling of HPV-stratified head and neck squamous cell carcinoma reveals distinct immune niches and microenvironmental architectures.Journal of translational medicine · 2025Article
- Lymphotoxin beta receptorInfection and immunity · 2025Article
- Complex interactions of cellular players in chronic Graft-versus-Host Disease.Frontiers in immunology · 2023Review
- Immunofibroblasts regulate LTα3 expression in tertiary lymphoid structures in a pathway dependent on ICOS/ICOSL interaction.Communications biology · 2022Article
- Lymphotoxin: from the physiology to the regeneration of the thymic function.Cell death and differentiation · 2021Review
- XBP-1s Promotes B Cell Pathogenicity in Chronic GVHD by Restraining the Activity of Regulated IRE-1α-Dependent Decay.Frontiers in immunology · 2021Article
- Autoantibodies as Diagnostic Markers and Mediator of Joint Inflammation in Arthritis.Mediators of inflammation · 2019Review
- Age-related impairment of humoral response to influenza is associated with changes in antigen specific T follicular helper cell responses.Scientific reports · 2016Article
- ICOS Co-Stimulation: Friend or Foe?Frontiers in immunology · 2016Review
- Article
- Lymphotoxin signalling in immune homeostasis and the control of microorganisms.Nature reviews. Immunology · 2013Review
- Fyn kinase is required for optimal humoral responses.PloS one · 2013Article
- Expression of inducible co-stimulator on peripheral blood T lymphocytes in patients with lupus nephritis.Rheumatology international · 2012Article
- Lymphotoxin-sensitive microenvironments in homeostasis and inflammation.Frontiers in immunology · 2012Article
- Article
- LTβR signaling in dendritic cells induces a type I IFN response that is required for optimal clonal expansion of CD8+ T cells.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Constitutive CD40L expression on B cells prematurely terminates germinal center response and leads to augmented plasma cell production in T cell areas.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- NF-kappaB pathways in the immune system: control of the germinal center reaction.Immunologic research · 2008Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
Germinal center (GC) responses to T-dependent Ags require effective collaboration between Th cells, activated B cells, and follicular dendritic cells within a highly organized microenvironment. Studies using gene-targeted mice have highlighted nonredundant molecules that are key for initiating and maintaining the GC niche, including the molecules of the ICOS, CD40, and lymphotoxin (LT) pathways. Signaling through ICOS has multiple consequences, including cytokine production, expression of CD40L on Th cells, and differentiation into CXCR5(+) follicular Th cells, all of which are important in the GC reaction. We have therefore taken advantage of ICOS(-/-) mice to dissect which downstream elements are required to initiate the formation of GC. In the context of a T-dependent immune response, we found that GC B cells from ICOS(-/-) mice express lower levels of LTalphabeta compared with wild-type GC B cells in vivo, and stimulation of ICOS on T cells induces LTalphabeta on B cells in vitro. Administration of agonistic anti-LTbeta receptor Ab was unable to restore the GC response in ICOS(-/-) mice, suggesting that additional input from another pathway is required for optimal GC generation. In contrast, treatment with agonistic anti-CD40 Ab in vivo recovered GC networks and restored LTalphabeta expression on GC B cells in ICOS(-/-) mice, and this effect was dependent on LTbeta receptor signaling. Collectively, these data demonstrate that ICOS activation is a prerequisite for the up-regulation of LTalphabeta on GC B cells in vivo and provide a model for cooperation between ICOS, CD40, and LT pathways in the context of the GC response.
Indexed as
Identifiers
What OpenQuestion holds
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.