Edinburgh Research Explorer

Reprogrammed quiescent B cells provide an effective cellular therapy against chronic experimental autoimmune encephalomyelitis

Research output: Contribution to journalArticle

  • Elisabeth Calderón-Gómez
  • Vicky Lampropoulou
  • Ping Shen
  • Patricia Neves
  • Toralf Roch
  • Ulrik Stervbo
  • Sascha Rutz
  • Anja A Kühl
  • Frank L Heppner
  • Christoph Loddenkemper
  • Stephen M Anderton
  • Jean M Kanellopoulos
  • Pierre Charneau
  • Simon Fillatreau

Related Edinburgh Organisations

Open Access permissions

Open

Documents

Original languageEnglish
Pages (from-to)1696-708
Number of pages13
JournalEuropean Journal of Immunology
Volume41
Issue number6
DOIs
Publication statusPublished - 2011

Abstract

Activated B cells can regulate immunity and have been envisaged as a potential cell-based therapy for treating autoimmune diseases. However, activated human B cells can also propagate immune responses, and the effects resulting from their infusion into patients cannot be predicted. This led us to consider resting B cells, which in contrast are poorly immunogenic, as an alternative cellular platform for the suppression of unwanted immunity. Here, we report that resting B cells can be directly engineered with lentiviral vectors to express antigens in a remarkably simple, rapid, and effective way. Notably, this neither required nor induced activation of the B cells. With this approach we were able to produce reprogrammed resting B cells that inhibited antigen-specific CD4(+) T cells, CD8(+) T cells, and B cells upon adoptive transfer in mice. Furthermore, resting B cells engineered to ectopically express myelin oligodendrocyte glycoprotein antigen protected recipient mice from severe disability and demyelination in EAE, and even induced complete remission from disease in mice lacking functional natural Tregs, which otherwise developed chronic paralysis. In conclusion, our study introduces reprogrammed quiescent B cells as a novel tool for suppressing undesirable immunity.

    Research areas

  • Adoptive Transfer, Animals, B-Lymphocytes, Cell Differentiation, Cell- and Tissue-Based Therapy, Cells, Cultured, Chronic Disease, Clonal Anergy, Disease Progression, Encephalomyelitis, Autoimmune, Experimental, Genetic Engineering, Humans, Immunosuppression, Interleukin-10/genetics, Mice, Mice, Knockout, Myelin Proteins, Myelin-Associated Glycoprotein, Myelin-Oligodendrocyte Glycoprotein, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory, Transgenes

Download statistics

No data available

ID: 3573230