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SMARCA5-mediated chromatin remodeling is required for germinal center formation

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F24%3A10485802" target="_blank" >RIV/00216208:11110/24:10485802 - isvavai.cz</a>

  • Result on the web

    <a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=pQ4b9Ax675" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=pQ4b9Ax675</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1084/jem.20240433" target="_blank" >10.1084/jem.20240433</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    SMARCA5-mediated chromatin remodeling is required for germinal center formation

  • Original language description

    B cells undergo extensive genomic reorganization during their proliferation and differentiation into germinal center and antibody-secreting cells. Stoler-Barak et al. demonstrate that SMARCA5, a component of the ISWI-complex, plays a critical role in gene accessibility and expression, facilitating the antibody-mediated immune response. The establishment of long-lasting immunity against pathogens is facilitated by the germinal center (GC) reaction, during which B cells increase their antibody affinity and differentiate into antibody-secreting cells (ASC) and memory cells. These events involve modifications in chromatin packaging that orchestrate the profound restructuring of gene expression networks that determine cell fate. While several chromatin remodelers were implicated in lymphocyte functions, less is known about SMARCA5. Here, using ribosomal pull-down for analyzing translated genes in GC B cells, coupled with functional experiments in mice, we identified SMARCA5 as a key chromatin remodeler in B cells. While the naive B cell compartment remained unaffected following conditional depletion of Smarca5, effective proliferation during B cell activation, immunoglobulin class switching, and as a result GC formation and ASC differentiation were impaired. Single-cell multiomic sequencing analyses revealed that SMARCA5 is crucial for facilitating the transcriptional modifications and genomic accessibility of genes that support B cell activation and differentiation. These findings offer novel insights into the functions of SMARCA5, which can be targeted in various human pathologies.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    10600 - Biological sciences

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2024

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Journal of Experimental Medicine

  • ISSN

    0022-1007

  • e-ISSN

    1540-9538

  • Volume of the periodical

    221

  • Issue of the periodical within the volume

    11

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    21

  • Pages from-to

    e20240433

  • UT code for WoS article

    001316111900001

  • EID of the result in the Scopus database

    2-s2.0-85204759274