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B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE261015 | GEO | 2024/09/01

REPOSITORIES: GEO

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B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling[Ribotag]

Project description: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, by using ribosomal pull-down for analyzing translated genes in GC B cells, coupled with functional experiments in mice, we identified SMARACA5 as a key chromatin remodeler in B cells. While the naive B cell compartment and early B cell activation remained unaffected following conditional depletion of Smarca5, immunoglobulin class switching, GC formation and ASC differentiation were impaired. Single-cell multi-omic sequencing analyses revealed that SMARCA5 is crucial for facilitating the transcriptional modifications and genomic accessibility of genes that support B cell differentiation. These findings offer novel insights into SMARCA5, which can be targeted in lymphoma patients.

2024-09-01 | GSE270216 | GEO

B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling[RNA-Seq]

2024-09-01 | GSE260882 | GEO

B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling[CUT & RUN]

2024-09-01 | GSE260881 | GEO

B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling[scMultiome - RNA + ATAC]

2024-09-01 | GSE261013 | GEO

B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling

Project description:B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling

| PRJNA1084819 | ENA

B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling[Ribotag]

Project description:B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling[Ribotag]

| PRJNA1125426 | ENA

B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling[RNA-Seq]

Project description:B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling[RNA-Seq]

| PRJNA1083906 | ENA

B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling[CUT & RUN]

Project description:B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling[CUT & RUN]

| PRJNA1083904 | ENA

B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling[scMultiome - RNA + ATAC]

Project description:B cell differentiation into germinal center and antibody-secreting cells depends on SMARCA5-mediated chromatin remodeling[scMultiome - RNA + ATAC]

| PRJNA1084825 | ENA

Pneumococcal polysaccharide abrogates conjugate-induced germinal center reaction and depletes antibody secreting cell pool, causing hyporesponsiveness.

Project description:BackgroundPlain pneumococcal polysaccharide (PPS) booster administered during second year of life has been shown to cause hyporesponsiveness. We assessed the effects of PPS booster on splenic memory B cell responses and persistence of PPS-specific long-lived plasma cells in the bone marrow (BM).MethodsNeonatal mice were primed subcutanously (s.c.) or intranasally (i.n.) with pneumococcal conjugate (Pnc1-TT) and the adjuvant LT-K63, and boosted with PPS+LT-K63 or saline 1, 2 or 3 times with 16 day intervals. Seven days after each booster, spleens were removed, germinal centers (GC), IgM(+), IgG(+) follicles and PPS-specific antibody secreting cells (AbSC) in spleen and BM enumerated.ResultsPPS booster s.c., but not i.n., compromised the Pnc1-TT-induced PPS-specific Abs by abrogating the Pnc1-TT-induced GC reaction and depleting PPS-specific AbSCs in spleen and limiting their homing to the BM. There was no difference in the frequency of PPS-specific AbSCs in spleen and BM between mice that received 1, 2 or 3 PPS boosters s.c.. Repeated PPS+LT-K63 booster i.n. reduced the frequency of PPS-specific IgG(+) AbSCs in BM.ConclusionsPPS booster-induced hyporesponsiveness is caused by abrogation of conjugate-induced GC reaction and depletion of PPS-specific IgG(+) AbSCs resulting in no homing of new PPS-specific long-lived plasma cells to the BM or survival. These results should be taken into account in design of vaccination schedules where polysaccharides are being considered.

| S-EPMC3771989 | biostudies-literature

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