Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 41, Issue 7, Pages 2107-2112Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201041315
Keywords
Autoantibody-secreting cells; Autoimmunity; Long-lived plasma cells; Lupus nephritis
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Funding
- German Research Society [FOR 831 TP 8, VO673/3-]
- Collaborative Research Center [SFB 643, B3]
- BayImmuNet program of the state of Bavaria
- Interdisciplinary Center for Clinical Research Erlangen (IZKF) [A31]
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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.
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