High frequency of autoantibody-secreting cells and long-lived plasma cells within inflamed kidneys of NZB/W F1 lupus mice

Eur J Immunol. 2011 Jul;41(7):2107-12. doi: 10.1002/eji.201041315. Epub 2011 Jun 6.

Abstract

Autoantibodies to double-stranded (ds) DNA represent a serological hallmark of systemic lupus erythematosus (SLE) and may critically contribute to the pathogenesis of lupus nephritis. Self-reactive antibodies might be partially produced by long-lived plasma cells (PCs), which mainly reside within the bone marrow and spleen. In contrast to short-lived PCs, long-lived PCs are extremely resistant to therapy and may sustain refractory disease courses. Recently, antibody-secreting cells were found within the inflamed kidneys of New Zealand black/white (NZB/W) F1 lupus mice as well as of patients with SLE. To analyze the longevity of the IgG-producing cells present in nephritic kidneys of NZB/W F1 mice we performed in vivo BrdU-labeling. We identified a higher frequency of long-lived than short-lived renal PCs, indicating that survival niches for long-lived PCs also exist within inflamed kidneys. Using ELISPOT assays, we found that on average 31% of renal IgG-producing cells reacted with dsDNA and 24% with nucleolin. Moreover, the frequencies of IgG-secreting cells specific for the autoantigens dsDNA and nucleolin were higher in the kidneys compared with those in the spleen and bone marrow.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / biosynthesis*
  • Antibodies, Antinuclear / immunology
  • Antibody-Producing Cells / immunology*
  • Autoantibodies / biosynthesis*
  • Autoantibodies / immunology
  • Bone Marrow / immunology
  • Bromodeoxyuridine / metabolism
  • Cell Survival
  • Enzyme-Linked Immunospot Assay
  • Female
  • Flow Cytometry
  • Immunoglobulin G / biosynthesis
  • Kidney / immunology*
  • Kidney / pathology
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / pathology
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / pathology
  • Mice
  • Mice, Inbred NZB
  • Phosphoproteins / immunology
  • Plasma Cells / immunology*
  • RNA-Binding Proteins / immunology
  • Spleen / immunology

Substances

  • Antibodies, Antinuclear
  • Autoantibodies
  • Immunoglobulin G
  • Phosphoproteins
  • RNA-Binding Proteins
  • nucleolin
  • Bromodeoxyuridine