A novel locus affecting serum levels of IgG2a maps to the murine <i> H2</i> region

Matthews, Vance B.; Christiansen, Frank; Price, Patricia

doi:10.1046/j.1365-2370.2000.00216.x

Cited by 8 publications

(17 citation statements)

References 32 publications

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“…Thus, the hypergammaglobulinemia of BALB.B mice mainly presents as a moderate elevation of IgG2a. This result is consistent with that of a previous study showing that H2 b mice with B10 or BALB/c backgrounds have higher serum levels of IgG2a than H2 k and H2 d congenic strains (27).…”

Section: Serum Levels Of Total Igm Igg1 and Igg2asupporting

confidence: 93%

The MHC Haplotype H2b Converts Two Pure Nonlupus Mouse Strains to Producers of Antinuclear Antibodies

Hannestad

Scott

2009

The Journal of Immunology

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Studies of mouse lupus models have linked the MHC H2b haplotype with the earlier appearance of antinuclear autoantibodies and the worsening of nephritis. However, it is unknown whether H2b by itself, in the context of pure nonlupus strains, is “silent” or sufficient with regard to loss of tolerance to chromatin (nucleosomes). In this study we show that, beginning ∼6–9 mo of age, H2b-congenic BALB/c (denoted BALB.B) mice, unlike BALB/c (H2d) and H2k-congenic BALB/c (denoted BALB.K) mice, develop strikingly increased serum levels of anti-chromatin Ab dominated by the IgG2a subclass, along with minor increase of Abs to DNA and moderately increased total serum IgG2a. The BALB.B mice did not have glomerulonephritis or an increased mortality rate. H2b-congenic C3H/He mice (designated C3.SW mice), unlike C3H/He (H2k) mice, showed low but measurable serum levels of chromatin-reactive IgG2a Abs and minor but significant hypergammaglobulinemia. By immunofluorescence, IgG2a of sera from both H2b-congenic strains stained HEp-2 cell nuclei, confirming the presence of antinuclear autoantibodies. Thus, in the context of two pure nonlupus genomes, the MHC H2b haplotype in homozygous form is sufficient to induce loss of tolerance to chromatin.

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Section: Serum Levels Of Total Igm Igg1 and Igg2asupporting

confidence: 93%

The MHC Haplotype H2b Converts Two Pure Nonlupus Mouse Strains to Producers of Antinuclear Antibodies

Hannestad

Scott

2009

The Journal of Immunology

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“…Here we describe studies of F2 and NOD congenic mice that confirm the mapping of Igis1 to the H2 region. Mice carrying the b allele of Igis1 had high basal levels of IgG2a, which suggests a bias towards T1 responses, 15 and this is consistent with a role in type I diabetes.…”

Section: Introductionsupporting

confidence: 53%

“…With the goat antimouse IgG2a coating antibody (Sigma: M‐8269) used throughout our studies and an antimouse IgG2c secondary antibody, 24 we determined that the IgG2a reactivity in sera from C57BL mice reflected levels of IgG2c. The effect of H2 haplotype on IgG2a levels 15 was evident with the IgG2c antibody ( H2 b = 100%; H2 k = 37%; H2 d = 62%; P < 0.03, Student's t ‐test; n = 6 mice per strain). According to common practice, the antibody detected in this communication will be designated IgG2a in all strains, but is actually IgG2c in C57BL and NOD mice.…”

Section: Methodsmentioning

confidence: 95%

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A locus affecting immunoglobulin isotype selection (Igis1) maps to the MHC region in C57BL, BALB/c and NOD mice

2001

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We have previously shown that H2b mice with B10 or BALB genetic backgrounds have higher basal levels of IgG2a than H2k and H2d congenic strains and, hence, have low IgG1/IgG2a ratios, which is consistent with a T1 cytokine milieu. The phenotypic marker of the high IgG2a levels, denoted immunoglobulin isotype‐1 (Igis1) was provisionally mapped telomeric of IEβ using MHC recombinant mice. In addition, data from B10.A(2R), B10.A(1R) and B10.A(18R) mice indicated that Igis1 may lie in a 27 kb region between G7b (Sm‐X5) and G7c. In the present study we confirm that Igis1 is in the H2 region using BALB and B10 congenic F2 mice. H2bb F2 mice had higher IgG2a levels than the H2dd parental strains. H2bd F1 and F2 mice on the B10 background produced IgG2a levels comparable with the H2bb parental strain, indicating that the b allele was dominant. In contrast, the H2bd F1 and F2 mice on the BALB background produced IgG2a levels between those of the H2bb and H2dd parental strains, indicating codominance of the b and d alleles. This suggests that a background gene influences regulation of IgG2a levels by Igis1. Non‐obese diabetic (NOD) mice (KdIAg7IEnu11Db), which can develop type 1 diabetes, had higher levels of IgG2a than NOD‐H2d congenic mice. Thus, Igis1 affects isotype selection in the presence of non‐MHC diabetes genes. As type 1 diabetes is associated with T1 responses, Igis1 may affect susceptibility to this condition.

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“…Recently, an association between H2 haplotype and serum IgG2a levels was demonstrated in H2 congenic B10 and BALB/c mice (48,49). The phenotypic marker of high IgG2a levels, denoted Ig isotype-1 (Igis1), was mapped to the central MHC class III region.…”

Section: Discussionmentioning

confidence: 99%

Role of MHC-Linked Genes in Autoantigen Selection and Renal Disease in a Murine Model of Systemic Lupus Erythematosus

Sekine

Graham

Zhao

et al. 2006

The Journal of Immunology

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We previously described a renal protective effect of factor B deficiency in MRL/lpr mice. Factor B is in the MHC cluster; thus, the deficient mice were H2b, the haplotype on which the knockout was derived, whereas the wild-type littermates were H2k, the H2 of MRL/lpr mice. To determine which protective effects were due to H2 vs factor B deficiency, we derived H2b congenic MRL/lpr mice from the 129/Sv (H2b) strain. Autoantibody profiling using autoantigen microarrays revealed that serum anti-Smith and anti-small nuclear ribonucleoprotein complex autoantibodies, while present in the majority of H2k/k MRL/lpr mice, were absent in the H2b/b MRL/lpr mice. Surprisingly, 70% of MRL/lpr H2b/b mice were found to be serum IgG3 deficient (with few to no IgG3-producing B cells). In addition, H2b/b IgG3-deficient MRL/lpr mice had significantly less proteinuria, decreased glomerular immune complex deposition, and absence of glomerular subepithelial deposits compared with MRL/lpr mice of any H2 type with detectable serum IgG3. Despite these differences, total histopathologic renal scores and survival were similar among the groups. These results indicate that genes encoded within or closely linked to the MHC region regulate autoantigen selection and isotype switching to IgG3 but have minimal effect on end-organ damage or survival in MRL/lpr mice.

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A novel locus affecting serum levels of IgG2a maps to the murine H2 region

Cited by 8 publications

References 32 publications

The MHC Haplotype H2b Converts Two Pure Nonlupus Mouse Strains to Producers of Antinuclear Antibodies

The MHC Haplotype H2b Converts Two Pure Nonlupus Mouse Strains to Producers of Antinuclear Antibodies

A locus affecting immunoglobulin isotype selection (Igis1) maps to the MHC region in C57BL, BALB/c and NOD mice

Role of MHC-Linked Genes in Autoantigen Selection and Renal Disease in a Murine Model of Systemic Lupus Erythematosus

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