β2-microglobulin is required for the full expression of xenobiotic-induced systemic autoimmunity

Kenneth M. Pollard, Per Hultman, Christopher B. Toomey, David M. Cauvi, Dwight H. Konoc

Research output: Contribution to journalArticlepeer-review

Abstract

Mercury exposure in both humans and mice is associated with features of systemic autoimmunity. Murine HgCl2-induced autoimmunity (mHgIA) requires MHC Class II, CD4 + T-cells, co-stimulatory molecules, and interferon-γ (IFN-γ), similar to spontaneous models of systemic lupus erythematosus (SLE). β2-microglobulin (B2m) is required for functional MHC Class I molecules and the neonatal Fc receptor (FcRn). 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 IgG1 subtype. Examination of IFNγ, 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 IgG1 anti-chromatin levels, and reduced IFNγ 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.

Original languageEnglish (US)
Pages (from-to)228-237
Number of pages10
JournalJournal of Immunotoxicology
Volume8
Issue number3
DOIs
StatePublished - Jul 2011
Externally publishedYes

Keywords

  • Autoantibodies
  • autoimmunity
  • cytokines
  • immune deposits
  • mercury
  • mouse
  • xenobiotic
  • β2-microglobulin

ASJC Scopus subject areas

  • Immunology
  • Toxicology

Fingerprint Dive into the research topics of 'β2-microglobulin is required for the full expression of xenobiotic-induced systemic autoimmunity'. Together they form a unique fingerprint.

Cite this