Depletion of B cells in murine lupus: efficacy and resistance

J Immunol. 2007 Sep 1;179(5):3351-61. doi: 10.4049/jimmunol.179.5.3351.


In mice, genetic deletion of B cells strongly suppresses systemic autoimmunity, providing a rationale for depleting B cells to treat autoimmunity. In fact, B cell depletion with rituximab is approved for rheumatoid arthritis patients, and clinical trials are underway for systemic lupus erythematosus. Yet, basic questions concerning mechanism, pathologic effect, and extent of B cell depletion cannot be easily studied in humans. To better understand how B cell depletion affects autoimmunity, we have generated a transgenic mouse expressing human CD20 on B cells in an autoimmune-prone MRL/MpJ-Fas(lpr) (MRL/lpr) background. Using high doses of a murine anti-human CD20 mAb, we were able to achieve significant depletion of B cells, which in turn markedly ameliorated clinical and histologic disease as well as antinuclear Ab and serum autoantibody levels. However, we also found that B cells were quite refractory to depletion in autoimmune-prone strains compared with non-autoimmune-prone strains. This was true with multiple anti-CD20 Abs, including a new anti-mouse CD20 Ab, and in several different autoimmune-prone strains. Thus, whereas successful B cell depletion is a promising therapy for lupus, at least some patients might be resistant to the therapy as a byproduct of the autoimmune condition itself.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20 / genetics
  • Antigens, CD20 / immunology*
  • Autoantibodies / blood
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • Cell Count
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Humans
  • Kidney Glomerulus / pathology
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / pathology
  • Lupus Erythematosus, Systemic / therapy*
  • Lymphocyte Depletion*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • Mice, Inbred MRL lpr
  • Mice, Transgenic
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology


  • 8H9 monoclonal antibody
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Autoantibodies