Article Text

Download PDFPDF

The early marginal zone B cell initiated T independent type 2 response resists the proteasome inhibitor bortezomib
  1. V Lang1,
  2. D Mielenz2,
  3. H Martin Jäck2,
  4. K Neubert1,
  5. C Böhm1,3,
  6. G Schett3,
  7. R E Voll1,3,
  8. S Meister1
  1. 1Interdisciplinary Center for Clinical Research, Research Group N2, Nikolaus Fiebiger-Center of Molecular Medicine, University Hospital Erlangen, Erlangen, Germany
  2. 2Division of Molecular Immunology, Department of Internal Medicine3, University of Erlangen-Nuremberg, Erlangen, Germany
  3. 3Department of Internal Medicine3 and Institute of Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany

Statistics from

The proteasome inhibitor bortezomib is clinically approved for the treatment of multiple myeloma. Recently, we demonstrated that bortezomib eliminates autoreactive plasma cells in SLE mice, thereby representing a promising novel treatment for antibody-mediated diseases. Here, we investigated the effect of bortezomib on the developing and pre-existing T dependent antibody response towards dinitrophenylated keyhole limpet hemocyanin and the T independent type 2 response towards NIP-Ficoll in BALB/c mice. Bortezomib treatment strongly reduced T dependent antibody titres mainly due to depletion of plasma cells. In contrast, the early T independent type 2 response, predominantly initiated by marginal zone (MZ) B cells, resisted bortezomib. Immunoproteasomal subunits and the antiapoptotic unfolded protein response were induced in NIP-Ficoll-stimulated MZ B cells after bortezomib treatment, but not in plasma cells. This induction might be cell autonomous and not a consequence of the microenvironment since mobilisation of MZ B cells out of the spleen did not render them susceptible towards bortezomib. We conclude that the resistance of MZ B cells against bortezomib leaves early T independent responses protecting against bloodborne pathogens largely intact. This fact may account for a relatively low risk of bacterial infections compared to most other immunosuppressants and cytotoxic drugs.

View Abstract

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.