ArticleThe Journal of experimental medicine2020
Syk degradation restrains plasma cell formation and promotes zonal transitions in germinal centers.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Fostamatinib for the treatment of warm antibody autoimmune hemolytic anemia: Phase 2, multicenter, open-label study.American journal of hematology · 2022Trial
- The B cell receptor-mTOR signaling axis restricts the accumulation of lung tissue-resident memory B cells after influenza infection.Science immunology · 2026Article
- Antigen receptor signaling and cell death resistance controls intestinal humoral response zonation.Immunity · 2023Article
- A novel selective spleen tyrosine kinase inhibitor SKI-O-703 (cevidoplenib) ameliorates lupus nephritis and serum-induced arthritis in murine models.Clinical and experimental immunology · 2023Article
- Competition for refueling rather than cyclic reentry initiation evident in germinal centers.Science immunology · 2022Article
- Supplying the trip to antibody production-nutrients, signaling, and the programming of cellular metabolism in the mature B lineage.Cellular & molecular immunology · 2022Review
- miR-15a/16-1 deletion in activated B cells promotes plasma cell and mature B-cell neoplasms.Blood · 2021Article
- Transcriptional regulation of memory B cell differentiation.Nature reviews. Immunology · 2021Review
- Article
- System-Level Scenarios for the Elucidation of T Cell-Mediated Germinal Center B Cell Differentiation.Frontiers in immunology · 2021Review
- Positive Selection in the Light Zone of Germinal Centers.Frontiers in immunology · 2021Review
- Multiscale Modeling of Germinal Center Recapitulates the Temporal Transition From Memory B Cells to Plasma Cells Differentiation as Regulated by Antigen Affinity-Based Tfh Cell Help.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Germinal centers (GCs) are sites at which B cells proliferate and mutate their antibody-encoding genes in the dark zone (DZ), followed by affinity-based selection in the light zone (LZ). B cell antigen receptor (BCR) signals induce Syk activation followed by rapid phosphatase-mediated desensitization; however, how degradation events regulate BCR functions in GCs is unclear. Here, we found that Syk degradation restrains plasma cell (PC) formation in GCs and promotes B cell LZ to DZ transition. Using a mouse model defective in Cbl-mediated Syk degradation, we demonstrate that this machinery attenuates BCR signaling intensity by mitigating the Kras/Erk and PI3K/Foxo1 pathways, and restricting the expression of PC transcription factors in GC B cells. Inhibition of Syk degradation perturbed gene expression, specifically in the LZ, and enhanced the generation of PCs without affecting B cell proliferation. These findings reveal how long-lasting attenuation of signal transduction by degradation events regulates cell fate within specialized microanatomical sites.
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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.