Idd-linked genetic regulation of TACIhigh expressing B cells in NOD mice

Sundström, Mia,1980-Umeå universitet,Immunologi/immunkemi,Kristina Lejon (författare)

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.

Lejon, KristinaUmeå universitet,Immunologi/immunkemi,Kristina Lejon(Swepub:umu)krle0001 (författare)
Umeå universitetImmunologi/immunkemi (creator_code:org_t)

Ingår i:Journal of Autoimmunity: Elsevier BV29:2-3, s. 116-1240896-84111095-9157

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