ArticleThe Journal of experimental medicine2016
Ubiquitin-mediated fluctuations in MHC class II facilitate efficient germinal center B cell responses.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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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.
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Who cites it
56 citing papers in PubMed, 80 citations in OpenAlex.
- Germinal Center Selection and Plasma Cell Differentiation.Immunological reviews · 2026Review
- A proximity ligation screen identifies SNAT2 as a novel target of the MARCH1 E3 ubiquitin ligase.Biology open · 2026Article
- The B-cell Receptor Blueprint in Lymphoma: Mechanisms and Therapeutic Opportunities.Blood cancer discovery · 2026Review
- Optimizing scheduling in dual-pulse nucleoside labeling experiments for cell-cycle analysis.Biophysical journal · 2026Article
- Intravital imaging of the formation and resolution of MHC class II-positive T-cell activation niches.Life science alliance · 2026Article
- B-cell peripheral tolerance: think dynamics beyond affinity.Frontiers in immunology · 2026Review
- T follicular helper cells transiently unlock a plasticity state in germinal centre B cells during the humoral immune response.Nature cell biology · 2026Article
- Major histocompatibility class II in murine antigen presenting cells is modified with a branched K63 and K11-linked ubiquitin chain.Scientific reports · 2025Article
- Review
- The role of ubiquitination in health and disease.MedComm · 2024Review
- The lipid globotriaosylceramide promotes germinal center B cell responses and antiviral immunity.Science (New York, N.Y.) · 2024Article
- Ubiquitin Signaling in the Immune System.Advances in experimental medicine and biology · 2024Review
- Pregnancy-related factors induce immune tolerance through regulation of sCD83 release.Frontiers in immunology · 2024Article
- Review
- Regulation of MHC class II and CD86 expression by March-I in immunity and disease.Current opinion in immunology · 2023Review
- The Ubiquitin Ligase Itch Skews Light Zone Selection in Germinal Centers.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Germinal center expansion but not plasmablast differentiation is proportional to peptide-MHCII density via CD40-CD40L signaling strength.Cell reports · 2022Article
- Competition for refueling rather than cyclic reentry initiation evident in germinal centers.Science immunology · 2022Article
- USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID.Signal transduction and targeted therapy · 2022Article
- The biology of the tumor microenvironment in DLBCL: Targeting the "don't eat me" signal.Journal of clinical and experimental hematopathology : JCEH · 2021Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
Antibody affinity maturation occurs in germinal centers (GCs) through iterative rounds of somatic hypermutation and selection. Selection involves B cells competing for T cell help based on the amount of antigen they capture and present on their MHC class II (MHCII) proteins. How GC B cells are able to rapidly and repeatedly transition between mutating their B cell receptor genes and then being selected shortly after is not known. We report that MHCII surface levels and degradation are dynamically regulated in GC B cells. Through ectopic expression of a photoconvertible MHCII-mKikGR chimeric gene, we found that individual GC B cells differed in the rates of MHCII protein turnover. Fluctuations in surface MHCII levels were dependent on ubiquitination and the E3 ligase March1. Increases in March1 expression in centroblasts correlated with decreases in surface MHCII levels, whereas CD83 expression in centrocytes helped to stabilize MHCII at that stage. Defects in MHCII ubiquitination caused GC B cells to accumulate greater amounts of a specific peptide-MHCII (pMHCII), suggesting that MHCII turnover facilitates the replacement of old complexes. We propose that pMHCII complexes are periodically targeted for degradation in centroblasts to favor the presentation of recently acquired antigens, thereby promoting the fidelity and efficiency of selection.
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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.