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

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.