B-cell gene therapy for tolerance induction: Host but not donor B-cell derived IL-10 is necessary for tolerance

Yan Su, Ai Hong Zhang, Nancy Noben-Trauth, David W. Scott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Genetically modified B cells are excellent tolerogenic antigen-presenting cells (APCs) in multiple models of autoimmunity. However, the mechanisms of action are still not completely understood. In our models, we generate antigen-specific tolerogenic B cells by transducing naïve or primed B cells with an antigen-immunoglobulin G (peptide-IgG) construct. In order to be transduced, B cells require activation with mitogens such as LPS. We and others have found that LPS stimulation of B cells upregulates the production of IL-10, a key cytokine for maintaining immune tolerance. In the current study, we defined the role of B-cell produced IL-10 in tolerance induction by using IL-10 deficient B cells as donor APCs. We found that peptide-IgG transduced IL-10 KO B cells have the same effects as wt B cells in tolerance induction in an experimental autoimmune encephalomyelitis model. Moreover, we demonstrated that the tolerogenic effect of peptide-IgG B cells was completely abrogated in anti-IL-10 receptor antibody treated recipients. Taken together, our results suggest that tolerance induced by peptide-IgG B-cell gene therapy requires IL-10 from the host but not donor B cells. These data shed important insights into the mechanisms of tolerance induction mediated by B-cell gene therapy.

Original languageEnglish
JournalFrontiers in Microbiology
Issue numberJULY
StatePublished - 2011
Externally publishedYes


  • B cells
  • Gene therapy
  • IL-10
  • IL-10 receptor
  • Tolerance


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