Abstract
Abstract B-cell delivered gene therapy has been useful for tolerance induction in several mouse models for autoimmune diseases. However, it is not known whether Ag specific B-cells can be transduced to serve as tolerogenic antigen-presenting cells (APC), since such cells would be present in primed hosts. To test this, LPS activated splenic B cells were transduced with a retroviral vector encoding the immunodominant peptide of myelin oligodendrocyte glycoprotein (MOG35-55) in frame with IgG (MOG-Ig). Unlike transduced B-cells from wild type C57Bl/6 (B6) donors, adoptive transfer of MOG-Ig transduced B-cells from MOG-specific BCR transgenic mice (αMOG B-cells) failed to ameliorate MOG35-55 induced EAE in either pretreatment or therapeutic protocols. However, αMOG B-cells transduced with control vector encoding OVA323-339 (OVA-Ig) were highly tolerogenic in terms of T-cell recall response to OVA323-339. Interestingly, significant protection in mice from EAE was observed when ~1% transduced αMOG B-cells were used in the EAE model (+99% MOG-Ig transduced B6 B-cells). These data suggested that Ag specific B-cells in nature can be transduced as tolerogenic APC when a non-relevant Ag was targeted, and Ag specific tolerance induction can still be achieved in the presence of low number of pathogenic antigen specific B-cells. (Supported by NIH grant RO1 AI035622 and a Pre-doctoral fellowship from the AHA)
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