Abnormal germinal center reactions in systemic lupus erythematosus demonstrated by blockade of CD154-CD40 interactions

J Clin Invest. 2003 Nov;112(10):1506-20. doi: 10.1172/JCI19301.


To determine the role of CD154-CD40 interactions in the B cell overactivity exhibited by patients with active systemic lupus erythematosus (SLE), CD19+ peripheral B cells were examined before and after treatment with humanized anti-CD154 mAb (BG9588, 5c8). Before treatment, SLE patients manifested activated B cells that expressed CD154, CD69, CD38, CD5, and CD27. Cells expressing CD38, CD5, or CD27 disappeared from the periphery during treatment with anti-CD154 mAb, and cells expressing CD69 and CD154 disappeared from the periphery during the post-treatment period. Before treatment, active-SLE patients had circulating CD38 (bright) Ig-secreting cells that were not found in normal individuals. Disappearance of this plasma cell subset during treatment was associated with decreases in anti-double-stranded DNA (anti-dsDNA) Ab levels, proteinuria, and SLE disease activity index. Consistent with this finding, peripheral B cells cultured in vitro spontaneously proliferated and secreted Ig in a manner that was inhibited by anti-CD154 mAb. Finally, the CD38(+/++)IgD(+), CD38(+++), and CD38(+)IgD(-) B cell subsets present in the peripheral blood also disappeared following treatment with humanized anti-CD154. Together, these results indicate that patients with active lupus nephritis exhibit abnormalities in the peripheral B cell compartment that are consistent with intensive germinal center activity, are driven via CD154-CD40 interactions, and may reflect or contribute to the propensity of these patients to produce autoantibodies.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / therapeutic use*
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • Biomarkers
  • CD4-Positive T-Lymphocytes / metabolism
  • CD40 Antigens / immunology
  • CD40 Antigens / metabolism*
  • CD40 Ligand / immunology*
  • CD40 Ligand / metabolism
  • Cells, Cultured
  • Female
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Germinal Center / metabolism*
  • Humans
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Lupus Erythematosus, Systemic / therapy*
  • Mice
  • Phenotype


  • Antibodies, Monoclonal
  • Biomarkers
  • CD40 Antigens
  • CD40 Ligand