SMARCA5-mediated chromatin remodeling is required for germinal center formation

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

SMARCA5-mediated chromatin remodeling is required for germinal center formation

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

SMARCA5-mediated chromatin remodeling is required for germinal center formation

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10600 - Biological sciences

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Journal of Experimental Medicine

ISSN

0022-1007

e-ISSN

1540-9538

Svazek periodika

221

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

21

Strana od-do

e20240433

Kód UT WoS článku

001316111900001

EID výsledku v databázi Scopus

2-s2.0-85204759274