GSE185487
Effect of the Idd2 locus of B10 origin on the transcriptome of B cell of NOD mice
Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic beta-cell destruction. It is a complex genetic trait driven by over 30 genetic loci with parallels between humans and mice. The NOD mouse spontaneously develops autoimmune diabetes and is widely used to identify insulin-dependent diabetes (Idd) genetic loci linked to diabetes susceptibility. While many Idd loci have been extensively studied, the impact of the Idd2 locus on autoimmune diabetes susceptibility remains to be defined. To address this, we generated a NOD congenic mouse bearing B10 resistance alleles on chromosome 9 in a locus coinciding with part of the Idd2 locus and find that NOD.B10-Idd2 congenic mice are highly resistant to diabetes. Bone marrow chimera and adoptive transfer experiments show that the B10 protective alleles provide resistance in an immune cell-intrinsic manner. While no T cell-intrinsic differences between NOD and NOD.B10-Idd2 mice were observed, we find that the Idd2 resistance alleles limit the formation of spontaneous and induced germinal centers. Comparison of the B cell transcriptome profile from NOD and NOD.B10-Idd2 mice reveal that resistance alleles at the Idd2 locus affect the expression of specific MHC molecules, a result confirmed by flow cytometry. Altogether, these data demonstrate that resistance alleles at the Idd2 locus impair germinal center formation and influence MHC expression, both of which likely contribute to reduce diabetes incidence. Overall design: 3 samples of isolated B and per mouse strain are analyzed. NOD cell samples serve as control.