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

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.

• Authors: 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
• Journal: European journal of immunology (Eur J Immunol) Vol. 41 Issue 6 Pg. 1696-708 (Jun 2011) ISSN: 1521-4141 [Electronic] Germany
• PMID: 21469107 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• MOG protein, human
• Mog protein, mouse
• Myelin Proteins
• Myelin-Associated Glycoprotein
• Myelin-Oligodendrocyte Glycoprotein
• Interleukin-10

Topics

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