Comparison of gene expression in NOD versus NOD.NOR-Chr4 (NR4) splenic B cells.

Type 1 Diabetes (T1D) in humans and the non-obese diabetic (NOD) mouse model results from autoreactive T cell destruction of pancreatic beta cells. A pathogenic role for B lymphocytes (B cells) in T1D first became evident when NOD mice made deficient in this population through introduction of an inactivated Ig heavy chain gene (NOD.Ignull) or chronic treatment with anti-IgM antibodies were strongly protected from disease. We produced an NOD background strain developing a greatly decreased T1D incidence due to a NOR-derived 44.31Mb congenic region from rs3674285 to D4Mit127 on distal Chr. 4 (termed NOD.NOR-Chr4 (NR4)) containing disease resistance alleles decreasing the pathogenic activity of autoreactive B cells. Microarrays were conducted on B cells purified from spleens of NOD and NR4 mice to highlight differentially expressed genes within the distal Chr. 4 locus. B cells were either cultured in media alone (unstimulated) or with BCR cross-linking anti-IgM-F(ab)2 fragments (stimulated) for 2h before RNA was extracted for transcript analysis.

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Stolp J, Chen YG, Cox SL, Henck V, Zhang W, Tsaih SW, Chapman H, Stearns T, Serreze DV, Silveira PA