Involvement of inducible costimulator in the exaggerated memory B cell and plasma cell generation in systemic lupus erythematosus

Arthritis Rheum. 2004 Oct;50(10):3211-20. doi: 10.1002/art.20519.


Objective: In systemic lupus erythematosus (SLE), the increased generation of memory B cells and plasma cells leads to autoimmune hypergammaglobulinemia and destructive immunoglobulin deposits in the kidneys. We undertook this study to determine the biologic mechanism driving this overactivation of the B cell compartment, which is the central issue in SLE.

Methods: We used flow cytometry to analyze expression of the T cell-specific inducible costimulator (ICOS) and its ligand (ICOS-L) on B cells obtained from the peripheral blood of SLE patients. We correlated ICOS-L expression with the differentiation status of the B cells using a large panel of surface antigens. In addition, SLE kidneys were analyzed by immunohistology.

Results: We found an increased expression of ICOS on CD4+ as well as CD8+ T cells in SLE. At the same time, we documented a down-regulation of ICOS-L on a high proportion of peripheral blood memory B cells. Based on in vitro experiments, we inferred that this ICOS-L down-regulation on B cells was a signature of recent interaction with ICOS+ T cells in vivo. In the kidneys of SLE patients, we found clusters of B cells and plasma cells in close contact with ICOS+ T cells.

Conclusion: Detailed analysis of B cells with down-regulated ICOS-L suggests that ICOS is one of the forces driving the formation of memory B cells and plasma cells in SLE. Furthermore, our identification of plasma cells in areas of T cell-B cell interaction in kidneys suggests that components of a T cell-driven B cell activation process may take place in peripheral tissues in SLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Antigens, Differentiation, T-Lymphocyte / physiology*
  • B-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Flow Cytometry
  • Humans
  • Immunologic Memory / physiology*
  • Inducible T-Cell Co-Stimulator Ligand
  • Inducible T-Cell Co-Stimulator Protein
  • Kidney / immunology
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Middle Aged
  • Plasma Cells / immunology*
  • Proteins / analysis
  • T-Lymphocytopenia, Idiopathic CD4-Positive / immunology


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • ICOS protein, human
  • ICOSLG protein, human
  • Inducible T-Cell Co-Stimulator Ligand
  • Inducible T-Cell Co-Stimulator Protein
  • Proteins