TY - JOUR
T1 - IL-21 promotes the production of anti-DNA IgG but is dispensable for kidney damage in lyn-/- mice
AU - Gutierrez, Toni
AU - Mayeux, Jessica M.
AU - Ortega, Sterling B.
AU - Karandikar, Nitin J.
AU - Li, Quan-zhen
AU - Rakheja, Dinesh
AU - Zhou, Xin J.
AU - Satterthwaite, Anne B
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
KW - Autoantibody
KW - Glomerulonephritis
KW - IL-21
KW - IL-6
KW - Lyn
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U2 - 10.1002/eji.201142095
DO - 10.1002/eji.201142095
M3 - Article
C2 - 23169140
AN - SCOPUS:84873750047
SN - 0014-2980
VL - 43
SP - 382
EP - 393
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 2
ER -