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Citations to this article

Genetic dissection of SLE pathogenesis. Sle1 on murine chromosome 1 leads to a selective loss of tolerance to H2A/H2B/DNA subnucleosomes.
C Mohan, … , P Yang, E K Wakeland
C Mohan, … , P Yang, E K Wakeland
Published March 15, 1998
Citation Information: J Clin Invest. 1998;101(6):1362-1372. https://doi.org/10.1172/JCI728.
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Research Article Article has an altmetric score of 5

Genetic dissection of SLE pathogenesis. Sle1 on murine chromosome 1 leads to a selective loss of tolerance to H2A/H2B/DNA subnucleosomes.

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Abstract

One of the hallmarks of SLE is the loss of tolerance to chromatin. The genes and mechanisms that trigger this loss of tolerance remain unknown. Our genetic studies in the NZM2410 lupus strain have implicated genomic intervals on chromosomes 1 (Sle1), 4 (Sle2), and 7 (Sle3) as conferring strong lupus susceptibility. Interestingly, B6 mice that are congenic for Sle1 (B6.NZMc1) have elevated IgG antichromatin Abs. This study explores the antinuclear antibody fine specificities and underlying cellular defects in these mice. On the B6 background, Sle1 by itself is sufficient to generate a robust, spontaneous antichromatin Ab response, staining Hep-2 nuclei homogeneously, and reacting primarily with H2A/H2B/DNA subnucleosomes. This targeted immune response peaks at 7-9 mo of age, affects both sexes with equally high penetrance (> 75%), and interestingly, does not "spread" to other subnucleosomal chromatin components. Sle1 also leads to an expanded pool of histone-reactive T cells, which may have a role in driving the anti-H2A/H2B/DNA B cells. However, these mice do not exhibit any generalized immunological defects or quantitative aberrations in lymphocyte apoptosis. We hypothesize that Sle1 may lead to the presentation of chromatin in an immunogenic fashion, or directly impact tolerance of chromatin-specific B cells.

Authors

C Mohan, E Alas, L Morel, P Yang, E K Wakeland

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Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 Total
Citations: 3 3 3 4 7 5 3 5 7 8 9 5 10 7 8 15 11 11 12 22 13 10 14 12 9 6 3 1 226
Citation information
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Citations to this article in year 2016 (7)

Title and authors Publication Year
Roles of CD48 in regulating immunity and tolerance
SL McArdel, C Terhorst, AH Sharpe
Clinical Immunology 2016
The Lupus Susceptibility Gene Pbx1 Regulates the Balance between Follicular Helper T Cell and Regulatory T Cell Differentiation
SC Choi, TE Hutchinson, AA Titov, HR Seay, S Li, TM Brusko, BP Croker, S Salek-Ardakani, L Morel
Journal of immunology (Baltimore, Md. : 1950) 2016
The SOD1 transgene expressed in erythroid cells alleviates fatal phenotype in congenic NZB/NZW-F1 mice
N Otsuki, T Konno, T Kurahashi, S Suzuki, J Lee, F Okada, Y Iuchi, T Homma, J Fujii
Free Radical Research 2016
Slamf6 negatively regulates autoimmunity
N Wang, M Keszei, P Halibozek, B Yigit, P Engel, C Terhorst
Clinical Immunology 2016
Alterations in nuclear structure promote lupus autoimmunity in a mouse model
N Singh, DB Johnstone, KA Martin, I Tempera, MJ Kaplan, MF Denny
Disease models & mechanisms 2016
Loss of Immune Tolerance Is Controlled by ICOS in Sle1 Mice
N Mittereder, E Kuta, G Bhat, K Dacosta, LI Cheng, R Herbst, G Carlesso
Journal of immunology (Baltimore, Md. : 1950) 2016
Slamf6 negatively regulates autoimmunity
N Wang, M Keszei, P Halibozek, B Yigit, P Engel, C Terhorst
Clinical Immunology 2016

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