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beta 2-microglobulin is required for the full expression of xenobiotic-induced systemic autoimmunity
Scripps Research Institute.
Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
Scripps Research Institute.
Scripps Research Institute.
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2011 (English)In: JOURNAL OF IMMUNOTOXICOLOGY, ISSN 1547-691X, Vol. 8, no 3, 228-237 p.Article in journal (Refereed) Published
Abstract [en]

ercury exposure in both humans and mice is associated with features of systemic autoimmunity. Murine HgCl(2)-induced autoimmunity (mHgIA) requires MHC Class II, CD4(+) T-cells, co-stimulatory molecules, and interferon-gamma (IFN-gamma), similar to spontaneous models of systemic lupus erythematosus (SLE). beta(2)-microglobulin (B2m) is required for functional MHC Class I molecules and the neonatal F(c) receptor (F(c)Rn). Deficiency of B2m in lupus-prone strains is consistently associated with reduced IgG levels, but with variable effects on other manifestations. Herein, we examined the role of B2m in mHgIA and show that in the absence of B2m, mercury-exposed mice failed to exhibit hypergammaglobulinemia, had reduced anti-nucleolar autoantibodies (ANoA), and had a lower incidence of immune complex deposits in splenic blood vessels, whereas IgG anti-chromatin autoantibodies and renal immune deposits were largely unaffected. Subclass analysis of the IgG anti-chromatin, however, revealed a significant reduction in the IgG(1) subtype. Examination of IFN gamma, IL-4, and IL-2 in exposed skin, draining lymph nodes, and spleen following mercury exposure showed reduced IL-4 in the spleen and skin in B2m-deficient mice, consistent with the lower IgG(1) anti-chromatin levels, and reduced IFN-gamma expression in the skin. These findings demonstrate how a single genetic alteration can partially but significantly modify the clinical manifestations of systemic autoimmunity induced by exposure to xenobiotics.

Place, publisher, year, edition, pages
Informa Healthcare , 2011. Vol. 8, no 3, 228-237 p.
Keyword [en]
Autoantibodies, autoimmunity, cytokines, immune deposits, mercury, beta 2-microglobulin, mouse, xenobiotic
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-69991DOI: 10.3109/1547691X.2011.583614ISI: 000293239100006OAI: diva2:433991
Available from: 2011-08-12 Created: 2011-08-12 Last updated: 2011-08-12

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Hultman, Per
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Molecular and Immunological PathologyFaculty of Health SciencesDepartment of Clinical Pathology and Clinical Genetics
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