A mouse model of systemic lupus erythematosus responds better to soluble TACI than to soluble BAFFR, correlating with depletion of plasma cells

Eur J Immunol. 2017 Jun;47(6):1075-1085. doi: 10.1002/eji.201746934. Epub 2017 Apr 24.

Abstract

The TNF family cytokines B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) support plasma cell survival. It is known that inhibitors of BAFF only (BAFFR-Fc) or BAFF and APRIL (TACI-Fc) administered early enough in an NZB/NZW F1 mouse model of systemic lupus erythematosus (SLE) ameliorate clinical outcomes, pointing to a pathogenic role of BAFF. In the present study, TACI-Fc administrated at a later stage of disease, after onset of autoimmunity, decreased the number of bone marrow plasma cells and slowed down further formation of autoantibodies. TACI-Fc prevented renal damage during a 12-week treatment period regardless of autoantibody levels, while BAFFR-Fc did not despite a similar BAFF-blocking activity in vivo. TACI-Fc also decreased established plasma cells in a T-dependent hapten/carrier immunization system better than single inhibitors of BAFF or APRIL, and sometimes better than combined single inhibitors with at least equivalent BAFF and APRIL inhibitory activities. These results indicate that TACI-Fc can prevent symptoms of renal damage in a mouse model of SLE when BAFFR-Fc cannot, and point to a plasticity of plasma cells for survival factors. Targeting plasma cells with TACI-Fc might be beneficial to prevent autoantibody-mediated damages in SLE.

Keywords: APRIL; BAFF/BLyS; Lupus; Plasma cell; SLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / biosynthesis
  • Autoimmunity
  • B-Cell Activating Factor / antagonists & inhibitors
  • B-Cell Activating Factor / immunology
  • B-Cell Activation Factor Receptor / administration & dosage
  • B-Cell Activation Factor Receptor / immunology
  • B-Lymphocytes / immunology
  • Disease Models, Animal*
  • Flow Cytometry
  • Kidney / immunology
  • Kidney / pathology
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / physiopathology
  • Lupus Erythematosus, Systemic / therapy
  • Mice
  • Plasma Cells / immunology*
  • Plasma Cells / pathology
  • Transmembrane Activator and CAML Interactor Protein / administration & dosage*
  • Transmembrane Activator and CAML Interactor Protein / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / antagonists & inhibitors
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / immunology

Substances

  • Autoantibodies
  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • Tnfrsf13b protein, mouse
  • Tnfrsf13c protein, mouse
  • Tnfsf13 protein, mouse
  • Tnfsf13b protein, mouse
  • Transmembrane Activator and CAML Interactor Protein
  • Tumor Necrosis Factor Ligand Superfamily Member 13