title: Gene therapy delivery of myelin oligodendrocyte glycoprotein (MOG) via hematopoietic stem cell transfer induces MOG-specific B cell deletion.
abstract: The 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 IgH(MOG) 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.
authors.affiliation: Department of Immunology, Central Clinical School, Monash University, Melbourne, Victoria 3181, Australia;
authors.forename: Jie-Yu
authors.initials: JY
authors.lastname: Chung
authors.forename: William
authors.initials: W
authors.lastname: Figgett
authors.forename: Kirsten
authors.initials: K
authors.lastname: Fairfax
authors.forename: Claude
authors.initials: C
authors.lastname: Bernard
authors.forename: James
authors.initials: J
authors.lastname: Chan
authors.forename: Ban-Hock
authors.initials: BH
authors.lastname: Toh
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mackay
authors.forename: Frank
authors.initials: F
authors.lastname: Alderuccio
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods*; D002478:Cells, Cultured; D017637:Clonal Deletion / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018183:Transplantation Chimera / Q000097:blood / Q000276:immunology
chemical_list: D063308:Myelin-Oligodendrocyte Glycoprotein