Transgene-mediated hyper-expression of IL-5 inhibits autoimmune disease but increases the risk of B cell chronic lymphocytic leukemia in a model of murine lupus

Eur J Immunol. 2004 Oct;34(10):2740-9. doi: 10.1002/eji.200425267.


IL-5 preferentially activates B1 cells to produce natural antibodies cross-reactive to self antigens. To determine the role of IL-5 in antibody-mediated autoimmune disease, we generated systemic lupus erythematosus (SLE)-prone (NZB x NZW)F1 mice congenic for IL-5 transgene (TG-F1). The transgene unexpectedly reduced the incidence of lupus nephritis. Anti-DNA antibodies in sera and those produced by splenic B cells in vitro were markedly decreased in TG-F1 mice, while total polyclonal Ig levels were comparable to those in IL-5 transgene-negative (NZB x NZW)F1 (non-TG-F1) littermates. Flow cytometry-sorted splenic B1 cells showed a significant reduction of anti-DNA antibody synthesis in response to IL-5, while proliferative responses to IL-5 did not significantly differ between TG-F1 and non-TG-F1 mice. As TG-F1 mice aged, frequencies of peripheral B1 cells progressively increased, and the mice frequently developed B cell chronic lymphocytic leukemia (B-CLL). Our results suggest that dysregulated, continuous high expression of IL-5 in SLE-prone mice may directly or indirectly mediate a skewed signaling of proliferation/differentiation of self-antigen-activated B1 cells, leading to suppression of autoimmune disease, but instead to aberrant expansion of B1 cells, giving rise to B-CLL. Thus, this model may provide a clue to the pathogenesis of both SLE and B-CLL.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / blood
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / immunology*
  • Blotting, Southern
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Interleukin-5 / genetics*
  • Interleukin-5 / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / etiology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Nephritis / immunology
  • Mice
  • Mice, Transgenic
  • Transgenes


  • Antibodies, Antinuclear
  • Immunoglobulin G
  • Immunoglobulin M
  • Interleukin-5