TY - JOUR
T1 - Role of MHC-linked genes in autoantigen selection and renal disease in a murine model of systemic lupus erythematosus
AU - Sekine, Hideharu
AU - Graham, Kareem L.
AU - Zhao, Shenre
AU - Elliott, Margaret K.
AU - Ruiz, Philip
AU - Utz, Paul J.
AU - Gilkeson, Gary S.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2006/11/15
Y1 - 2006/11/15
N2 - 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. Autoaatibody 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.
AB - 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. Autoaatibody 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.
UR - http://www.scopus.com/inward/record.url?scp=33750816202&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750816202&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.177.10.7423
DO - 10.4049/jimmunol.177.10.7423
M3 - Article
C2 - 17082662
AN - SCOPUS:33750816202
VL - 177
SP - 7423
EP - 7434
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -