Inhibition of the CD40-CD40ligand pathway prevents murine membranous glomerulonephritis

Kidney Int. 1995 Aug;48(2):458-68. doi: 10.1038/ki.1995.314.


Several forms of glomerulonephritis are induced by antibodies against self or foreign antigens. Normal B lymphocyte antibody production requires T cell costimulatory signals provided in part by T cell surface expression of gp39/CD40ligand (CD40L) that engages the B cell receptor CD40 and induces B cell differentiation and immunoglobulin class switching. We assessed the effect of disrupting the CD40L-CD40 costimulatory pathway, using a CD40-Ig fusion protein, on the development of membranous glomerulonephritis (MGN) in the mouse. MGN is induced by mouse antibodies that recognize and bind to exogenously administered rabbit anti-mouse renal tubular brush border (RbAMBB) IgG immobilized in the glomerular capillary wall. MGN did not occur in nude mice, showing the need of the T cell function. C57Bl/10 mice immunized with RbAMBB and treated with CD40-Ig fusion protein displayed a delayed autologous response and absence of MGN lesions, while control fusion proteins failed to prevent the development of the disease. These observations provide evidence that disruption of the CD40-CD40L costimulatory pathway can prevent the development of MGN by suppressing T cell-dependent antibody production.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Base Sequence
  • CD40 Antigens / genetics
  • CD40 Antigens / metabolism*
  • Fluorescent Antibody Technique
  • Glomerulonephritis, Membranous / metabolism
  • Glomerulonephritis, Membranous / pathology
  • Glomerulonephritis, Membranous / prevention & control*
  • Immunoglobulins / genetics
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Ligands
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron
  • Molecular Probes / genetics
  • Molecular Sequence Data
  • Rabbits
  • Recombinant Fusion Proteins / pharmacology
  • Solubility


  • Antibodies, Monoclonal
  • CD40 Antigens
  • Immunoglobulins
  • Ligands
  • Molecular Probes
  • Recombinant Fusion Proteins