IL-21 promotes the production of anti-DNA IgG but is dispensable for kidney damage in lyn-/- mice

Toni Gutierrez, Jessica M. Mayeux, Sterling B. Ortega, Nitin J. Karandikar, Quan-zhen Li, Dinesh Rakheja, Xin J. Zhou, Anne B Satterthwaite

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The autoimmune disease systemic lupus erythematosus is characterized by loss of tolerance to nuclear Ags and a heightened inflammatory environment, which together result in end organ damage. Lyn-deficient mice, a model of systemic lupus erythematosus, lack an inhibitor of B-cell and myeloid cell activation. This results in B-cell hyper-responsiveness, plasma cell accumulation, autoantibodies, and glomerulonephritis (GN). IL-21 is associated with autoimmunity in mice and humans and promotes B-cell differentiation and class switching. Here, we explore the role of IL-21 in the autoimmune phenotypes of lyn-/- mice. We find that IL-21 mRNA is reduced in the spleens of lyn-/-IL-6-/- and lyn-/-Btklo mice, neither of which produce pathogenic autoantibodies or develop significant GN. While IL-21 is dispensable for plasma cell accumulation and IgM autoantibodies in lyn-/- mice, it is required for anti-DNA IgG antibodies and some aspects of T-cell activation. Surprisingly, GN still develops in lyn-/-IL-21-/- mice. This likely results from the presence of IgG autoantibodies against a limited set of non-DNA Ags. These studies identify a specific role for IL-21 in the class switching of anti-DNA B cells and demonstrate that neither IL-21 nor anti-DNA IgG is required for kidney damage in lyn-/- mice.

Original languageEnglish (US)
Pages (from-to)382-393
Number of pages12
JournalEuropean Journal of Immunology
Volume43
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Autoantibody
  • Glomerulonephritis
  • IL-21
  • IL-6
  • Lyn

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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