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Regulation of germinal center B-cell homeostasis by Deltex-1 (Dtx1) [scRNA]

ABSTRACT: Germinal centers (GC) are sites for the clonal expansion and affinity maturation of B-cells that is coordinated by interaction with follicular dendritic cells (fDCs) and T follicular helper (TFH) cells. Loss of GC homeostasis can contribute to the development of B-cell malignancies and autoimmunity. Here we sought to investigate the GC-specific function of Deltex-1 (Dtx1), a gene that is highly expressed in GC B-cells and is a prominent target of aberrant somatic hypermutation. Dtx1 conditional knock-out (cKO) led to a competitive advantage in the GC reaction and marked GC hyperplasia accompanied by expansion of, and dependence upon, the fDC network. Dtx1 cKO GC B-cells bore transcriptional evidence of Notch and Myc pathway activation, and genetic inhibition of Notch activity led to resolution of GC hyperplasia. Together, these data implicate Dtx1 as a critical regulator of fDC-derived Notch signaling and GC homeostasis.

ORGANISM(S): Mus musculus

PROVIDER: GSE293902 | GEO | 2026/04/04

REPOSITORIES: GEO

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Regulation of germinal center B-cell homeostasis by Deltex-1 (Dtx1) [scBCR]

Project description:Germinal centers (GC) are sites for the clonal expansion and affinity maturation of B-cells that is coordinated by interaction with follicular dendritic cells (fDCs) and T follicular helper (TFH) cells. Loss of GC homeostasis can contribute to the development of B-cell malignancies and autoimmunity. Here we sought to investigate the GC-specific function of Deltex-1 (Dtx1), a gene that is highly expressed in GC B-cells and is a prominent target of aberrant somatic hypermutation. Dtx1 conditional knock-out (cKO) led to a competitive advantage in the GC reaction and marked GC hyperplasia accompanied by expansion of, and dependence upon, the fDC network. Dtx1 cKO GC B-cells bore transcriptional evidence of Notch and Myc pathway activation, and genetic inhibition of Notch activity led to resolution of GC hyperplasia. Together, these data implicate Dtx1 as a critical regulator of fDC-derived Notch signaling and GC homeostasis.

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