Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 41, Issue 6, Pages 1696-1708Publisher
WILEY
DOI: 10.1002/eji.201041041
Keywords
Autoimmunity; B cells; Cellular therapy; Gene therapy; Lentiviral vector
Categories
Funding
- Hertie Stiftung
- Association de Recherche sur la Sclerose en Plaques (ARSEP)
- Deutsche Forschungsgemeinschaft [SFB-650, SFB TRR43, Exc 25]
- US National Institutes of Health (NINDS) [R01 NS046006]
- Medical research Council (MRC)
- Medical Research Council [G9900991B, G0901697, G0801924] Funding Source: researchfish
- MRC [G0901697, G0801924] Funding Source: UKRI
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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.
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