Dampening Ab responses using proteasome inhibitors following in vivo B cell activation

Paolo Cascio, Laura Oliva, Fulvia Cerruti, Elisabetta Mariani, Elena Pasqualetto, Simone Cenci, Roberto Sitia

Research output: Contribution to journalArticlepeer-review

Abstract

Upon encounter with Ag, B lymphocytes undergo terminal differentiation into plasma cells, highly specialized Ab secretors that mediate humoral immune responses. Profound changes adapt cellular morphology and proteome to the new secretory functions. Although a massive secretory activity is expected to require an efficient ubiquitin-proteasome degradation system, recent in vitro studies have surprisingly revealed that the proteasome function sharply decreases during plasma cell development, thereby limiting the proteolytic capacity. We challenged this paradigm in mouse models of B cell activation, and observed that following polyclonal activation, proteasome activity decreases more than previously reported in vitro. This decrease is linked to enhanced apoptosis after treatment with the potent anti-myeloma proteasome inhibitor PS-341. Accordingly, in vivo treatment with PS-341 decreases Ab titres in T-dependent and -independent mouse immunization models. This study provides the rationale for limiting the activity of Ab-secreting cells in vivo by impacting proteasome function.

Original languageEnglish
Pages (from-to)658-667
Number of pages10
JournalEuropean Journal of Immunology
Volume38
Issue number3
DOIs
Publication statusPublished - Mar 2008

Keywords

  • Antibodies
  • Apoptosis
  • B cells
  • Cell differentiation
  • Proteasomes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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