Interferon-α induces unabated production of short-lived plasma cells in pre-autoimmune lupus-prone (NZB×NZW)F1 mice but not in BALB/c mice

Eur J Immunol. 2011 Mar;41(3):863-72. doi: 10.1002/eji.201040649. Epub 2011 Feb 11.


IFN-α is known to play a critical role in the pathogenesis of systemic lupus erythematosus (SLE), but the mechanisms remain unclear. We previously showed that within weeks, exposure to IFN-α in vivo induces lupus in pre-autoimmune lupus-prone NZB×NZW F1 (NZB/W) but not in BALB/c mice. In the current study, we show that in vivo expression of IFN-α induces sustained B-cell proliferation in both BALB/c and NZB/W mice. In NZB/W but not BALB/c mice, B-cell proliferation was accompanied by a rapid and unabated production of autoantibody-secreting cells (ASCs) in secondary lymphoid organs, suggesting that a B-cell checkpoint is altered in the autoimmune background. The majority (>95%) of ASCs elicited in IFN-α-treated NZB/W mice were short-lived and occurred without the induction of long-lived plasma cells. A short course of cyclophosphamide caused a sharp drop in IFN-α-elicited short-lived plasma cells, but the levels recovered within days following termination of treatment. Thus, our work provides new insights into effectiveness and limitations of the current SLE therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody-Producing Cells / drug effects
  • Antibody-Producing Cells / immunology
  • Antibody-Producing Cells / pathology
  • Autoimmunity / drug effects
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / pathology
  • Cyclophosphamide / pharmacology
  • Female
  • Immunosuppressive Agents / pharmacology
  • Interferon Type I / genetics
  • Interferon Type I / pharmacology*
  • Lupus Erythematosus, Systemic / etiology*
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred NZB
  • Plasma Cells / drug effects*
  • Plasma Cells / immunology*
  • Plasma Cells / pathology
  • Recombinant Proteins
  • Species Specificity


  • Immunosuppressive Agents
  • Interferon Type I
  • Recombinant Proteins
  • Cyclophosphamide