Dichotomous effects of complete versus partial class II major histocompatibility complex deficiency on circulating autoantibody levels in autoimmune‐prone mice

Stohl, William; Xu, Dong; Metzger, Troy E.; Kim, Kyoung Soo; Morel, Laurence; Kotzin, Brian L.

doi:10.1002/art.20359

Cited by 14 publications

(19 citation statements)

References 41 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Serum total IgG levels in non-Tg B6.Sle1 and B6.Nba2 mice were greater (geometric mean 29-96%) than in non-Tg B6 mice (P Ͻ 0.001) ( Figure 2C). These serologic results paralleled those previously observed for corresponding mice tested at 8-9 months of age (38).…”

Section: Numbers Of Splenic T Cells and B Cells And Globalsupporting

confidence: 89%

“…By 8-9 months of age, large percentages of B6.Sle1 and B6.Nba2 mice harbor detectable circulating IgG antichromatin autoantibodies (32)(33)(34)38). By 3 months of age, there was already a significant difference in serum levels of IgG antichromatin in the B6 mice compared with the B6.Sle1 and the B6.Nba2 mice (P Ͻ 0.001) ( Figure 2D).…”

Section: Numbers Of Splenic T Cells and B Cells And Globalmentioning

confidence: 94%

“…Mice transgenic for murine BAFF (21) that had been backcrossed to B6 mice for Ͼ9 generations (B6.BAFF mice) were maintained as hemizygotes for the BAFF Tg. B6.Sle1.BAFF and B6.Nba2.BAFF mice were generated by crossing B6.Sle1 and B6.Nba2 mice (31,32,38), respectively, with B6.BAFF mice and screening the F 1 progeny (obligate heterozygotes for the Sle1 and Nba2 regions, respectively) for the BAFF Tg by polymerase chain reaction (PCR) (see below). F 1 mice bearing the BAFF Tg were backcrossed to B6.Sle1 and B6.Nba2 mice, and the resulting pups were screened for homozygosity for the Sle1 and Nba2 regions, respectively, by PCR (38) and for the BAFF Tg.…”

Section: Methodsmentioning

confidence: 99%

“…Serum levels of IgG autoantibodies to chromatin and dsDNA were determined by ELISA (38). Quantitative values were obtained by use of standard curves obtained with monoclonal antibodies to the appropriate nuclear antigen (42).…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

BAFF overexpression and accelerated glomerular disease in mice with an incomplete genetic predisposition to systemic lupus erythematosus

Stohl¹,

Xu²,

Kim³

et al. 2005

Arthritis & Rheumatism

Self Cite

104

View full text Add to dashboard Cite

Objective. To determine whether overexpression of BAFF can accelerate the development of systemic lupus erythematosus-associated end-organ disease in hosts with an underlying autoimmune diathesis.Methods. We introduced a BAFF transgene (Tg) into autoimmune-prone B6.Sle1 and B6.Nba2 mice and evaluated these mice for serologic autoimmunity and renal pathology.Results Conclusion. BAFF-driven effects on glomerular pathology may be mediated, at least in part, by autoantibodies with specificities other than chromatin and/or by autoantibody-independent means. There is an uncoupling of BAFF-driven precocious glomerular pathology from concomitant development of clinically apparent renal disease, strongly suggesting that BAFF overexpression works in concert with other factors to promote overt renal disease.Renal involvement in patients with systemic lupus erythematosus (SLE) is clinically apparent in ϳ50% of cases and leads to considerable morbidity. The vast majority of SLE patients with renal involvement develop increased proteinuria, sometimes to degrees great enough to adversely affect systemic fluid balance and hemodynamics (nephrotic syndrome). Glomerular disease is widely believed to be the major contributor to this increased proteinuria. Indeed, the World Health Organization (WHO) classification of lupus nephritis focuses almost entirely on glomerular lesions, with little attention to tubular, interstitial, or vascular lesions. Accordingly, factors which promote glomerular disease in SLE may be vital to the pathogenesis of lupus nephritis.

show abstract

Section: Numbers Of Splenic T Cells and B Cells And Globalsupporting

confidence: 89%

Section: Numbers Of Splenic T Cells and B Cells And Globalmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

BAFF overexpression and accelerated glomerular disease in mice with an incomplete genetic predisposition to systemic lupus erythematosus

Stohl¹,

Xu²,

Kim³

et al. 2005

Arthritis & Rheumatism

Self Cite

104

View full text Add to dashboard Cite

show abstract

“…[30][31][32][33] Analyses of splenocytes from 4-to 5-month-and 11-month-old IFNAR þ / þ , IFNAR þ /À and IFNAR À/À mice showed less of a shift with age in the ratio of memory-to-naive CD4 þ T cells in IFNAR-deficient mice. We have previously shown that IFNab are important for the maintenance, but not the activation, of CD4 þ T cells.…”

Section: Discussionmentioning

confidence: 99%

Type I interferon signaling is involved in the spontaneous development of lupus-like disease in B6.Nba2 and (B6.Nba2 × NZW)F1 mice

et al. 2007

View full text Add to dashboard Cite

Several studies have described a role for type I interferons (IFNab) in the initiation and/or prolongation of autoimmune diseases. Most pronounced has been the association of disease activity with what is now known as 'the interferon signature' of gene expression in peripheral blood mononuclear cells from lupus patients. In correlation, studies have shown that inhibition of IFNab signaling abrogates disease in various mouse models of lupus. New Zealand black (NZB) and B6.Nba2 congenic mice spontaneously develop elevated levels of serum anti-nuclear autoantibodies (ANAs). Nevertheless, neither of these strains develop fatal renal disease. The female F1 offspring of NZB or B6.Nba2 crossed with New Zealand white (NZW) mice do, however, develop kidney disease. We have previously shown that increases in endogenous IFNab levels in (B6.Nba2 Â NZW)F1 mice leads to accelerated development of renal disease in an IFNab-dependent manner. We now show that B6.Nba2 and (B6.Nba2 Â NZW)F1 mice deficient for the IFNab-receptor fail to develop ANA and renal disease, although the mice have substantial immune complex deposition in the glomeruli. Thus, endogenous IFNab might influence disease by affecting B-cell activation and differentiation, as well as the kidneys' susceptibility to damage, the latter perhaps through induction of a local inflammatory milieu.

show abstract

Constitutive overexpression of BAFF in autoimmune‐resistant mice drives only some aspects of systemic lupus erythematosus–like autoimmunity

Stohl¹,

Jacob²,

Guo³

et al. 2010

Arthritis & Rheumatism

Self Cite

View full text Add to dashboard Cite

Objective. To determine whether overexpression of BAFF can promote systemic lupus erythematosus (SLE)-like autoimmunity in mice that are otherwise autoimmune-resistant.Methods. We used class II major histocompatibility complex (MHC)-deficient C57BL/6 (B6) mice as a model of resistance to SLE and Sles1-bearing B6 mice as a model of resistance to the autoantibody-promoting capacity of the Sle1 region. We generated BAFFtransgenic (Tg) counterparts to these respective mice and evaluated lymphocyte phenotype, serologic autoimmunity, renal immunopathology, and clinical disease in the BAFF-Tg and non-Tg mouse sets.Results. Although constitutive BAFF overexpression did not lead to B cell expansion in class II MHC-deficient B6 mice, it did lead to increased serum IgG autoantibody levels. Nevertheless, renal immunopathology was limited, and clinical disease did not develop. In B6 and B6.Sle1 mice, constitutive BAFF overexpression led to increased numbers of B cells and CD4؉ memory cells, as well as increased serum IgG and IgA autoantibody levels. Renal immunopathology was modestly greater in BAFF-Tg mice than in their non-Tg counterparts, but again, clinical disease did not develop.

show abstract

Dichotomous effects of complete versus partial class II major histocompatibility complex deficiency on circulating autoantibody levels in autoimmune‐prone mice

Abstract: Objective. To assess the effects of altered class II major histocompatibility complex (MHCII) expression on circulating autoantibody levels in C57BL/6 (B6) mice congenic for the Sle1 (B6.Sle1 mice) or Nba2 (B6.Nba2 mice) regions. Methods. H-2Ab

Cited by 14 publications

References 41 publications

BAFF overexpression and accelerated glomerular disease in mice with an incomplete genetic predisposition to systemic lupus erythematosus

BAFF overexpression and accelerated glomerular disease in mice with an incomplete genetic predisposition to systemic lupus erythematosus

Type I interferon signaling is involved in the spontaneous development of lupus-like disease in B6.Nba2 and (B6.Nba2 × NZW)F1 mice

Constitutive overexpression of BAFF in autoimmune‐resistant mice drives only some aspects of systemic lupus erythematosus–like autoimmunity

Contact Info

Product

Resources

About