B Cell Diversification Is Uncoupled from SAP-Mediated Selection Forces in Chronic Germinal Centers within Peyer's Patches.


:Antibodies secreted within the intestinal tract provide protection from the invasion of microbes into the host tissues. Germinal center (GC) formation in lymph nodes and spleen strictly requires SLAM-associated protein (SAP)-mediated T cell functions; however, it is not known whether this mechanism plays a similar role in mucosal-associated lymphoid tissues. Here, we find that in Peyer's patches (PPs), SAP-mediated T cell help is required for promoting B cell selection in GCs, but not for clonal diversification. PPs of SAP-deficient mice host chronic GCs that are absent in T cell-deficient mice. GC B cells in SAP-deficient mice express AID and Bcl6 and generate plasma cells in proportion to the GC size. Single-cell IgA sequencing analysis reveals that these mice host few diversified clones that were subjected to mild selection forces. These findings demonstrate that T cell-derived help to B cells in PPs includes SAP-dependent and SAP-independent functions.


Cell Rep


Cell reports


Biram A,Winter E,Denton AE,Zaretsky I,Dassa B,Bemark M,Linterman MA,Yaari G,Shulman Z




Has Abstract


2020-02-11 00:00:00












  • DNA-PK Is Targeted by Multiple Vaccinia Virus Proteins to Inhibit DNA Sensing.

    abstract::Virus infection is sensed by pattern recognition receptors (PRRs) detecting virus nucleic acids and initiating an innate immune response. DNA-dependent protein kinase (DNA-PK) is a PRR that binds cytosolic DNA and is antagonized by vaccinia virus (VACV) protein C16. Here, VACV protein C4 is also shown to antagonize DN...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Scutts SR,Ember SW,Ren H,Ye C,Lovejoy CA,Mazzon M,Veyer DL,Sumner RP,Smith GL

    更新日期:2018-11-13 00:00:00

  • 5-Hydroxymethylcytosine Remodeling Precedes Lineage Specification during Differentiation of Human CD4(+) T Cells.

    abstract::5-methylcytosine (5mC) is converted to 5-hydroxymethylcytosine (5hmC) by the TET family of enzymes as part of a recently discovered active DNA de-methylation pathway. 5hmC plays important roles in regulation of gene expression and differentiation and has been implicated in T cell malignancies and autoimmunity. Here, w...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Nestor CE,Lentini A,Hägg Nilsson C,Gawel DR,Gustafsson M,Mattson L,Wang H,Rundquist O,Meehan RR,Klocke B,Seifert M,Hauck SM,Laumen H,Zhang H,Benson M

    更新日期:2016-07-12 00:00:00

  • CAST/ELKS Proteins Control Voltage-Gated Ca2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse.

    abstract::In the presynaptic terminal, the magnitude and location of Ca2+ entry through voltage-gated Ca2+ channels (VGCCs) regulate the efficacy of neurotransmitter release. However, how presynaptic active zone proteins control mammalian VGCC levels and organization is unclear. To address this, we deleted the CAST/ELKS protein...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Dong W,Radulovic T,Goral RO,Thomas C,Suarez Montesinos M,Guerrero-Given D,Hagiwara A,Putzke T,Hida Y,Abe M,Sakimura K,Kamasawa N,Ohtsuka T,Young SM Jr

    更新日期:2018-07-10 00:00:00

  • Combinatorial Smad2/3 Activities Downstream of Nodal Signaling Maintain Embryonic/Extra-Embryonic Cell Identities during Lineage Priming.

    abstract::Epiblast cells in the early post-implantation stage mammalian embryo undergo a transition described as lineage priming before cell fate allocation, but signaling pathways acting upstream remain ill defined. Genetic studies demonstrate that Smad2/3 double-mutant mouse embryos die shortly after implantation. To learn mo...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Senft AD,Costello I,King HW,Mould AW,Bikoff EK,Robertson EJ

    更新日期:2018-08-21 00:00:00

  • Direct Binding between Pre-S1 and TRP-like Domains in TRPP Channels Mediates Gating and Functional Regulation by PIP2.

    abstract::Transient receptor potential (TRP) channels are regulated by diverse stimuli comprising thermal, chemical, and mechanical modalities. They are also commonly regulated by phosphatidylinositol-4,5-bisphosphate (PIP2), with underlying mechanisms largely unknown. We here revealed an intramolecular interaction of the TRPP3...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Zheng W,Cai R,Hofmann L,Nesin V,Hu Q,Long W,Fatehi M,Liu X,Hussein S,Kong T,Li J,Light PE,Tang J,Flockerzi V,Tsiokas L,Chen XZ

    更新日期:2018-02-06 00:00:00

  • Spontaneous Vesicle Fusion Is Differentially Regulated at Cholinergic and GABAergic Synapses.

    abstract::The locomotion of C. elegans is balanced by excitatory and inhibitory neurotransmitter release at neuromuscular junctions. However, the molecular mechanisms that maintain the balance of synaptic transmission remain enigmatic. Here, we investigated the function of voltage-gated Ca2+ channels in triggering spontaneous r...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Liu H,Li L,Wang W,Gong J,Yang X,Hu Z

    更新日期:2018-02-27 00:00:00

  • Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes.

    abstract::During development, two cell types born from closely related progenitor pools often express identical transcriptional regulators despite their completely distinct characteristics. This phenomenon implies the need for a mechanism that operates to segregate the identities of the two cell types throughout differentiation...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Clovis YM,Seo SY,Kwon JS,Rhee JC,Yeo S,Lee JW,Lee S,Lee SK

    更新日期:2016-08-09 00:00:00

  • Metoclopramide treatment blocks CD93-signaling-mediated self-renewal of chronic myeloid leukemia stem cells.

    abstract::Self-renewal is a key characteristic of leukemia stem cells (LSCs) responsible for the development and maintenance of leukemia. In this study, we identify CD93 as an important regulator of self-renewal and proliferation of murine and human LSCs, but not hematopoietic stem cells (HSCs). The intracellular domain of CD93...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Riether C,Radpour R,Kallen NM,Bürgin DT,Bachmann C,Schürch CM,Lüthi U,Arambasic M,Hoppe S,Albers CE,Baerlocher GM,Ochsenbein AF

    更新日期:2021-01-26 00:00:00

  • Two mechanisms produce mutation hotspots at DNA breaks in Escherichia coli.

    abstract::Mutation hotspots and showers occur across phylogeny and profoundly influence genome evolution, yet the mechanisms that produce hotspots remain obscure. We report that DNA double-strand breaks (DSBs) provoke mutation hotspots via stress-induced mutation in Escherichia coli. With tet reporters placed 2 kb to 2 Mb (half...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Shee C,Gibson JL,Rosenberg SM

    更新日期:2012-10-25 00:00:00

  • Proteomic Profiling of Mammalian COPII and COPI Vesicles.

    abstract::Intracellular transport and homeostasis of the endomembrane system in eukaryotic cells depend on the formation and fusion of vesicular carriers. Coat protein complex (COP) II vesicles export newly synthesized secretory proteins from the endoplasmic reticulum (ER), whereas COPI vesicles facilitate traffic from the Golg...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Adolf F,Rhiel M,Hessling B,Gao Q,Hellwig A,Béthune J,Wieland FT

    更新日期:2019-01-02 00:00:00

  • Transforming growth factor β/activin signaling functions as a sugar-sensing feedback loop to regulate digestive enzyme expression.

    abstract::Organisms need to assess their nutritional state and adapt their digestive capacity to the demands for various nutrients. Modulation of digestive enzyme production represents a rational step to regulate nutriment uptake. However, the role of digestion in nutrient homeostasis has been largely neglected. In this study, ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Chng WA,Sleiman MSB,Schüpfer F,Lemaitre B

    更新日期:2014-10-09 00:00:00

  • CRISPR-Cas9 Ribonucleoprotein-Mediated Genomic Editing in Mature Primary Innate Immune Cells.

    abstract::CRISPR genome engineering has become a powerful tool to functionally investigate the complex mechanisms of immune system regulation. While decades of work have aimed to genetically reprogram innate immunity, the utility of current approaches is restricted by poor knockout efficiencies or limited specificity for mature...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Riggan L,Hildreth AD,Rolot M,Wong YY,Satyadi W,Sun R,Huerta C,O'Sullivan TE

    更新日期:2020-05-19 00:00:00

  • The Anti-Warburg Effect Elicited by the cAMP-PGC1α Pathway Drives Differentiation of Glioblastoma Cells into Astrocytes.

    abstract::Glioblastoma multiforme (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed as a potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established an induced differentiation model of GBM using cAMP activators that ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Xing F,Luan Y,Cai J,Wu S,Mai J,Gu J,Zhang H,Li K,Lin Y,Xiao X,Liang J,Li Y,Chen W,Tan Y,Sheng L,Lu B,Lu W,Gao M,Qiu P,Su X,Yin W,Hu J,Chen Z,Sai K,Wang J,Chen F,Chen Y,Zhu S,Liu D,Cheng S,Xie Z

    更新日期:2017-01-10 00:00:00

  • Mechanistic Insights into Cofactor-Dependent Coupling of RNA Folding and mRNA Transcription/Translation by a Cobalamin Riboswitch.

    abstract::Riboswitches are mRNA elements regulating gene expression in response to direct binding of a metabolite. While these RNAs are increasingly well understood with respect to interactions between receptor domains and their cognate effector molecules, little is known about the specific mechanistic relationship between meta...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Polaski JT,Holmstrom ED,Nesbitt DJ,Batey RT

    更新日期:2016-05-03 00:00:00

  • αKlotho Regulates Age-Associated Vascular Calcification and Lifespan in Zebrafish.

    abstract::The hormone αKlotho regulates lifespan in mice, as knockouts die early of what appears to be accelerated aging due to hyperphosphatemia and soft tissue calcification. In contrast, the overexpression of αKlotho increases lifespan. Given the severe mouse phenotype, we generated zebrafish mutants for αklotho as well as i...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Singh AP,Sosa MX,Fang J,Shanmukhappa SK,Hubaud A,Fawcett CH,Molind GJ,Tsai T,Capodieci P,Wetzel K,Sanchez E,Wang G,Coble M,Tang W,Cadena SM,Fishman MC,Glass DJ

    更新日期:2019-09-10 00:00:00

  • Lineage-Specific and Non-specific Cytokine-Sensing Genes Respond Differentially to the Master Regulator STAT5.

    abstract::STAT5, a member of the family of signal transducers and activators of transcription, senses cytokines and controls the biology of cell lineages, including mammary, liver, and T cells. Here, we show that STAT5 activates lineage-specific and widely expressed genes through different mechanisms. STAT5 preferentially binds...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Zeng X,Willi M,Shin HY,Hennighausen L,Wang C

    更新日期:2016-12-20 00:00:00

  • TRIP13 Functions in the Establishment of the Spindle Assembly Checkpoint by Replenishing O-MAD2.

    abstract::The spindle assembly checkpoint (SAC) prevents premature segregation of chromosomes during mitosis. This process requires structural remodeling of MAD2 from O-MAD2 to C-MAD2 conformation. After the checkpoint is satisfied, C-MAD2 is reverted to O-MAD2 to allow anaphase-promoting complex/cyclosome (APC/C) to trigger an...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Ma HT,Poon RYC

    更新日期:2018-02-06 00:00:00

  • An in vivo chemical genetic screen identifies phosphodiesterase 4 as a pharmacological target for hedgehog signaling inhibition.

    abstract::Hedgehog (Hh) signaling plays an integral role in vertebrate development, and its dysregulation has been accepted widely as a driver of numerous malignancies. While a variety of small molecules target Smoothened (Smo) as a strategy for Hh inhibition, Smo gain-of-function mutations have limited their clinical implement...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Williams CH,Hempel JE,Hao J,Frist AY,Williams MM,Fleming JT,Sulikowski GA,Cooper MK,Chiang C,Hong CC

    更新日期:2015-04-07 00:00:00

  • Structures of NS5 Methyltransferase from Zika Virus.

    abstract::The Zika virus (ZIKV) poses a major public health emergency. To aid in the development of antivirals, we present two high-resolution crystal structures of the ZIKV NS5 methyltransferase: one bound to S-adenosylmethionine (SAM) and the other bound to SAM and 7-methyl guanosine diphosphate (7-MeGpp). We identify feature...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Coloma J,Jain R,Rajashankar KR,García-Sastre A,Aggarwal AK

    更新日期:2016-09-20 00:00:00

  • Neuronal Soma-Derived Degradative Lysosomes Are Continuously Delivered to Distal Axons to Maintain Local Degradation Capacity.

    abstract::Neurons face the challenge of maintaining cellular homeostasis through lysosomal degradation. While enzymatically active degradative lysosomes are enriched in the soma, their axonal trafficking and positioning and impact on axonal physiology remain elusive. Here, we characterized axon-targeted delivery of degradative ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Farfel-Becker T,Roney JC,Cheng XT,Li S,Cuddy SR,Sheng ZH

    更新日期:2019-07-02 00:00:00

  • Disruption of the Interaction of RAS with PI 3-Kinase Induces Regression of EGFR-Mutant-Driven Lung Cancer.

    abstract::RAS family GTPases contribute directly to the regulation of type I phosphoinositide 3-kinases (PI3Ks) via RAS-binding domains in the PI3K catalytic p110 subunits. Disruption of this domain of p110α impairs RAS-mutant-oncogene-driven tumor formation and maintenance. Here, we test the effect of blocking the interaction ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Murillo MM,Rana S,Spencer-Dene B,Nye E,Stamp G,Downward J

    更新日期:2018-12-26 00:00:00

  • Engraftment of embryonic stem cells and differentiated progeny by host conditioning with total lymphoid irradiation and regulatory T cells.

    abstract::Embryonic stem cells (ESCs) hold promise for the treatment of many medical conditions; however, their utility is limited by immune rejection. The objective of our study is to establish tolerance or promote engraftment of transplanted ESCs as well as mature cell populations derived from ESCs. Luciferase (luc(+))-expres...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Pan Y,Leveson-Gower DB,de Almeida PE,Pierini A,Baker J,Florek M,Nishikii H,Kim BS,Ke R,Wu JC,Negrin RS

    更新日期:2015-03-24 00:00:00

  • The immunodominant and neutralization linear epitopes for SARS-CoV-2.

    abstract::Although vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are under development, the antigen epitopes on the virus and their immunogenicity are poorly understood. Here, we simulate the 3D structures and predict the B cell epitopes on the spike (S), envelope (E), membrane (M), and nucleocap...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Lu S,Xie XX,Zhao L,Wang B,Zhu J,Yang TR,Yang GW,Ji M,Lv CP,Xue J,Dai EH,Fu XM,Liu DQ,Zhang L,Hou SJ,Yu XL,Wang YL,Gao HX,Shi XH,Ke CW,Ke BX,Jiang CG,Liu RT

    更新日期:2021-01-26 00:00:00

  • The MARCH6-SQLE Axis Controls Endothelial Cholesterol Homeostasis and Angiogenic Sprouting.

    abstract::The endothelial monolayer forms a barrier between the lumen of blood vessels and the underlying tissues. Stable VE-cadherin-based adherens junctions are essential for maintaining this barrier, whereas their remodeling is required for angiogenesis in health and disease. Here, we position the ERAD-associated ubiquitin l...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Tan JME,van der Stoel MM,van den Berg M,van Loon NM,Moeton M,Scholl E,van der Wel NN,Kovačević I,Hordijk PL,Loregger A,Huveneers S,Zelcer N

    更新日期:2020-08-04 00:00:00

  • Mpn1, mutated in poikiloderma with neutropenia protein 1, is a conserved 3'-to-5' RNA exonuclease processing U6 small nuclear RNA.

    abstract::Clericuzio-type poikiloderma with neutropenia (PN) is a rare genodermatosis associated with mutations in the C16orf57 gene, which codes for the uncharacterized protein hMpn1. We show here that, in both fission yeasts and humans, Mpn1 processes the spliceosomal U6 small nuclear RNA (snRNA) posttranscriptionally. In Mpn...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Shchepachev V,Wischnewski H,Missiaglia E,Soneson C,Azzalin CM

    更新日期:2012-10-25 00:00:00

  • Bruton's tyrosine kinase phosphorylates DDX41 and activates its binding of dsDNA and STING to initiate type 1 interferon response.

    abstract::The innate immune system senses cytosolic dsDNA and bacterial cyclic dinucleotides and initiates signaling via the adaptor STING to induce type 1 interferon (IFN) response. We demonstrate here that BTK-deficient cells have impaired IFN-β production and TBK1/IRF3 activation when stimulated with agonists or infected wit...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Lee KG,Kim SS,Kui L,Voon DC,Mauduit M,Bist P,Bi X,Pereira NA,Liu C,Sukumaran B,Rénia L,Ito Y,Lam KP

    更新日期:2015-02-24 00:00:00

  • Roof Plate-Derived Radial Glial-like Cells Support Developmental Growth of Rapidly Adapting Mechanoreceptor Ascending Axons.

    abstract::Spinal cord longitudinal axons comprise some of the longest axons in our body. However, mechanisms that drive this extra long-distance axonal growth are largely unclear. We found that ascending axons of rapidly adapting (RA) mechanoreceptors closely abut a previously undescribed population of roof plate-derived radial...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Kridsada K,Niu J,Haldipur P,Wang Z,Ding L,Li JJ,Lindgren AG,Herrera E,Thomas GM,Chizhikov VV,Millen KJ,Luo W

    更新日期:2018-06-05 00:00:00

  • The RNA helicase DHX34 activates NMD by promoting a transition from the surveillance to the decay-inducing complex.

    abstract::Nonsense-mediated decay (NMD) is a surveillance mechanism that degrades aberrant mRNAs. A complex comprising SMG1, UPF1, and the translation termination factors eRF1 and eRF3 (SURF) is assembled in the vicinity of a premature termination codon. Subsequently, an interaction with UPF2, UPF3b, and the exon junction compl...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Hug N,Cáceres JF

    更新日期:2014-09-25 00:00:00

  • GNA11 Q209L Mouse Model Reveals RasGRP3 as an Essential Signaling Node in Uveal Melanoma.

    abstract::Uveal melanoma (UM) is characterized by mutually exclusive activating mutations in GNAQ, GNA11, CYSLTR2, and PLCB4, four genes in a linear pathway to activation of PLCβ in almost all tumors and loss of BAP1 in the aggressive subset. We generated mice with melanocyte-specific expression of GNA11Q209L with and without h...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Moore AR,Ran L,Guan Y,Sher JJ,Hitchman TD,Zhang JQ,Hwang C,Walzak EG,Shoushtari AN,Monette S,Murali R,Wiesner T,Griewank KG,Chi P,Chen Y

    更新日期:2018-02-27 00:00:00

  • Zfp281 Shapes the Transcriptome of Trophoblast Stem Cells and Is Essential for Placental Development.

    abstract::Placental development is a key event in mammalian reproduction and embryogenesis. However, the molecular basis underlying placental development is not fully understood. Here, we conduct a forward genetic screen to identify regulators for extraembryonic development and identify Zfp281 as a key factor. Zfp281 overexpres...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Ishiuchi T,Ohishi H,Sato T,Kamimura S,Yorino M,Abe S,Suzuki A,Wakayama T,Suyama M,Sasaki H

    更新日期:2019-05-07 00:00:00