Analysis of V_HGene Utilisation in the Non-Obese Diabetic Mouse

Abstract

The immunoglobulin (Ig) heavy chain variable (VH) gene complexity and the VH gene utilisation pattern of the non-obese diabetic (NOD) mouse were investigated. We found that the NOD mouse displays a VH gene complexity which appears to be identical to that of the C57BL/6 mouse. Thus, Southern hybridisation using probes specific for 9 of the murine VH gene families revealed identical restriction fragment length polymorphism (RFLP) patterns in both mouse strains. As indicated by immunofluorescence analysis using allotype specific monoclonal antibodies the NOD mice were also found to carry the IgCH-1b allele. Collectively, these data suggest that the NOD mice carry an IgVH locus identical to that carried by C57BL/6. In contrast to the apparent identity at the level of germline VH gene repertoires, the pattern of VH gene utilisation differed considerably between these two mouse strains. Thus, in NOD mice the neonatal preference of D-proximal VH genes was found to be more pronounced than in C57BL/6 mice. Moreover, in contrast to adult C57BL/6 mice a D-proximal bias was evident also in adult NOD mice. On the basis of these findings we discuss the possibility that the distorted development of B cell repertoires in the NOD mouse could be directly or indirectly related to the T cell mediated, autoimmune process in the NOD mouse.

Multiple Germline κ Light Chains Generate Anti-Insulin B Cells in Nonobese Diabetic Mice

“…Although NOD was not included in that study, our data strongly support the hypothesis that NOD and NZB share the Ig b haplotype. This is not the case for Ig H chains, as studies clearly indicate that the H chain loci of NOD and C57BL/6 mice are highly similar, if not identical (44,45). Interestingly, in the D'Hoostelaere study, NZB was the only strain of the 55 investigated that exhibited the b haplotype.…”

The prolonged and enhanced immune response in the non-obese diabetic mouse is dependent on genes in the Idd1/24, Idd12 and Idd18 regions

“…We [14] and others [15e17] have demonstrated that the immune response in NOD mice is enhanced and prolonged, and often leads to anaphylaxis upon re-challenge with the antigen, both using foreign and self antigens, including allotypic immunoglobulins [18]. Moreover, we have demonstrated that NOD mice have a disordered V H gene utilization pattern [19] which is in line with that the early B cell repertoire is spontaneously activated [20] and/ or possibly exhibit a selection defect [21]. Additional B cell alterations in the NOD mouse include altered expression of TACI [22] as well exaggerated Ig-complex binding [23].…”

Uncoupling of Anergy from Developmental Arrest in Anti-Insulin B Cells Supports the Development of Autoimmune Diabetes

“…Previous studies suggest that the B cell repertoire of NOD mice is subject to selection defects and may not be generated normally (26,27); therefore, the expression of IgM alleles on B cells from NOD and B6 mice harboring 125Tg anti-insulin (IgM a ) was examined. As shown in Fig.…”