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Smc3 regulates B-cell transit through germinal centers and restricts their malignant transformation

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

ORGANISM(S): Mus musculus

PROVIDER: GSE143852 | GEO | 2020/10/13

REPOSITORIES: GEO

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Smc3 dosage regulates B cell transit through germinal centers and restricts their malignant transformation.

Project description: Not available

| S-EPMC7855695 | biostudies-literature

Smc3 regulates B-cell transit through germinal centers and restricts their malignant transformation (HiC)

Project description:During the germinal center (GC) reaction, B-cells undergo extensive redistribution of cohesin complex and 3D re-organization of their genomes. Yet, the significance of cohesin and architectural programming in the humoral immune response is unknown. Herein we report that conditional homozygous deletion of cohesin subunit Smc3 abrogated GC formation, yet in marked contrast, Smc3 haploinsufficiency induced GC hyperplasia, skewing of GC polarity and impaired plasma cell differentiation. Transcriptional and architectural profiling revealed defects in GC terminal differentiation programs controlled by lymphoma epigenetic tumor suppressors Tet2 and Kmt2d, and failure of Smc3+/- GC B-cells to switch from B-cell to plasma cell lineage factors. There was also impaired connectivity of gene regulatory elements controlling tumor suppressor genes, and accordingly Smc3 haploinsufficiency accelerated lymphomagenesis in mice with constitutive Bcl6 expression. Collectively, our data indicate a dose dependent function for cohesin in humoral immunity to facilitate the B-cell to plasma cell lineage switch, while restricting their malignant transformation.

2020-10-13 | GSE143853 | GEO