Bone marrow of NZB/W mice is the major site for plasma cells resistant to dexamethasone and cyclophosphamide: implications for the treatment of autoimmunity

J Autoimmun. 2012 Sep;39(3):180-8. doi: 10.1016/j.jaut.2012.05.010. Epub 2012 Jun 20.


Antibodies contribute to the pathogenesis of many chronic inflammatory diseases, including autoimmune disorders and allergies. They are secreted by proliferating plasmablasts, short-lived plasma cells and non-proliferating, long-lived memory plasma cells. Memory plasma cells refractory to immunosuppression are critical for the maintenance of both protective and pathogenic antibody titers. Here, we studied the response of plasma cells in spleen, bone marrow and inflamed kidneys of lupus-prone NZB/W mice to high-dose dexamethasone and/or cyclophosphamide. BrdU+, dividing plasmablasts and short-lived plasma cells in the spleen were depleted while BrdU- memory plasma cells survived. In contrast, all bone marrow plasma cells including anti-DNA secreting cells were refractory to both drugs. Unlike bone marrow and spleen, which showed a predominance of IgM-secreting plasma cells, inflamed kidneys mainly accommodated IgG-secreting plasma cells, including anti-DNA secreting cells, some of which survived the treatments. These results indicate that the bone marrow is the major site of memory plasma cells resistant to treatment with glucocorticoids and anti-proliferative drugs, and that inflamed tissues and secondary lymphoid organs can contribute to the autoreactive plasma cell memory. Therefore, new strategies targeting autoreactive plasma cell memory should be considered. This could be the key to finding a curative approach to the treatment of chronic inflammatory autoantibody-mediated diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / biosynthesis
  • Autoantibodies / immunology
  • Autoimmunity / drug effects
  • Bone Marrow / drug effects
  • Bone Marrow / immunology*
  • Bone Marrow / pathology
  • Bromodeoxyuridine / administration & dosage
  • Cyclophosphamide / pharmacology
  • Cyclophosphamide / therapeutic use*
  • DNA / immunology
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use*
  • Disease Models, Animal
  • Female
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / immunology
  • Immunoglobulin M / biosynthesis
  • Immunoglobulin M / immunology
  • Immunologic Memory / drug effects
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / drug effects
  • Kidney / immunology
  • Kidney / pathology
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / immunology
  • Lupus Nephritis / pathology
  • Mice
  • Mice, Inbred NZB
  • Organ Specificity
  • Plasma Cells / drug effects
  • Plasma Cells / immunology*
  • Plasma Cells / pathology
  • Spleen / drug effects
  • Spleen / immunology
  • Spleen / pathology


  • Autoantibodies
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunosuppressive Agents
  • Dexamethasone
  • Cyclophosphamide
  • DNA
  • Bromodeoxyuridine