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Gene therapy delivery of myelin oligodendrocyte glycoprotein (MOG) via hematopoietic stem cell transfer induces MOG-specific B cell deletion
journal contribution
posted on 2023-05-20, 06:57 authored by Chung, JY, Figgett, W, Kirsten FairfaxKirsten Fairfax, Bernard, C, Chan, J, Toh, BH, Mackay, F, Alderuccio, FThe various mechanisms that have been described for immune tolerance govern our ability to control self-reactivity and minimize autoimmunity. However, the capacity to genetically manipulate the immune system provides a powerful avenue to supplement this natural tolerance in an Ag-specific manner. We have previously shown in the mouse model of experimental autoimmune encephalomyelitis that transfer of bone marrow (BM) transduced with retrovirus encoding myelin oligodendrocyte glycoprotein (MOG) promotes disease resistance and CD4(+) T cell deletion within the thymus. However, the consequence of this strategy on B cell tolerance is not known. Using BM from IgHMOG mice that develop MOG-specific B cell receptors, we generated mixed chimeras together with BM-encoding MOG. In these animals, the development of MOG-specific B cells was abrogated, resulting in a lack of MOG-specific B cells in all B cell compartments examined. This finding adds a further dimension to our understanding of the mechanisms of tolerance that are associated with this gene therapy approach to treating autoimmunity and may have important implications for Ab-mediated autoimmune disorders.
History
Publication title
Journal of ImmunologyVolume
192Issue
6Pagination
2593-2601ISSN
0022-1767Department/School
Menzies Institute for Medical ResearchPublisher
Amer Assoc ImmunologistsPlace of publication
9650 Rockville Pike, Bethesda, USA, Md, 20814Rights statement
Copyright 2014 The American Association of Immunologists, Inc.Repository Status
- Restricted