Idd-linked genetic regulation of TACIhigh expressing B cells in NOD mice.
In NOD mice, B cells play a key role in the initiation of type 1 diabetes pathogenesis. We have identified a novel NOD-specific B cell-related trait, i.e. the increased percentage of TACI(high)-expressing splenic B cells, by comparing NOD mice with non-autoimmune C57BL/6 mice. Using athymic NOD mice, we determined that this trait was T cell independent. We mapped the loci contributing to the increased proportion of TACI(high) expressing splenic B cells and found that the control of TACI expression was strongly linked to chromosome 1, in a region which includes the insulin-dependent diabetes (Idd) 5 loci. Moreover, another locus potentially involved was detected in the vicinity of Idd22 on chromosome 8. Interestingly, when analyzing age-dependent contribution to the obtained LOD scores we observed that the linkage to chromosome 8 was explained solely by mice > or =61 days of age, suggesting a temporal genetic regulation of TACI expression. In addition, analysis of genetic interaction between chromosome 1 and chromosome 8 indicated that the two loci acted in an additive fashion. Our findings corroborate the notion that B cell deviations contribute to type 1 diabetes development, and suggest a temporal regulation of TACI(high) expression, possibly influenced by the ongoing autoimmune process.
Sundström
Mia
M
Umeå University, Department of Clinical Microbiology, Division of Immunology, SE-901 87 Umeå, Sweden.
Lejon
Kristina
K
D000818:Animals; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D008126:Lod Score; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D013154:Spleen; D053303:Transmembrane Activator and CAML Interactor Protein / Q000276:immunology* / Q000378:metabolism*
C486361:Tnfrsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein