{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/30822"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/30822","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Meningeal B cells in central nervous system autoimmunity: Their phenotype and susceptibility to therapeutic depletion","abstract":"B cell depleting therapies have been effective in the treatment of Multiple Sclerosis (MS), yet to date little is known about how B cells promote disease pathogenesis. B cells can be found invading the meninges around the brain and spinal cord in MS, where they cluster in association with T cells. These meningeal B cells clusters are often adjacent to demyelinating lesions suggesting this may be a site where B cells are exerting their pathogenic effects. The purpose of this thesis was to understand the contribution of meningeal B cells to central nervous system (CNS) autoimmunity, by characterizing their phenotype and determining their susceptibility to B cell depletion. Using an animal model of MS, immunofluorescence analysis, flow cytometry, or single-cell sequencing analysis was used to analyze B cells within the inflamed CNS. Interestingly, while anti-myelin T cells were readily identified in the inflamed CNS, anti-myelin B cells were excluded from this site. Non-specific B cells within the CNS were phenotypically unique from naïve B cells, exhibiting a non-classical activation status. Following treatment with anti-CD20, B cells were rapidly depleted in peripheral tissues such as the blood, lymph node and spleen, while depletion in the CNS was delayed. Following treatment there was minimal evidence that anti-CD20 accessed meningeal B cells directly, but rather that depletion was indirect and the result of ongoing turnover of the meningeal population and elimination of the peripheral pool from which it is sustained. Depleting B cells from the CNS resulted in significantly less demyelination and T cell accumulation within meningeal clusters. This suggests that B cells may be required to help with T cell reactivation within the meninges, and that depletion of B cells over time prevents ongoing local pathology. Collectively, this thesis elucidates the phenotype of B cells within the inflamed CNS of anti-myelin autoimmunity, supporting a role for their involvement in disease pathogenesis. By selectively targeting pathogenic populations of B cells this will help minimize the adverse effects that exist with current complete B cell depletion therapies.","abstract_html":"B cell depleting therapies have been effective in the treatment of Multiple Sclerosis (MS), yet to date little is known about how B cells promote disease pathogenesis. B cells can be found invading the meninges around the brain and spinal cord in MS, where they cluster in association with T cells. These meningeal B cells clusters are often adjacent to demyelinating lesions suggesting this may be a site where B cells are exerting their pathogenic effects. The purpose of this thesis was to understand the contribution of meningeal B cells to central nervous system (CNS) autoimmunity, by characterizing their phenotype and determining their susceptibility to B cell depletion. Using an animal model of MS, immunofluorescence analysis, flow cytometry, or single-cell sequencing analysis was used to analyze B cells within the inflamed CNS. Interestingly, while anti-myelin T cells were readily identified in the inflamed CNS, anti-myelin B cells were excluded from this site. Non-specific B cells within the CNS were phenotypically unique from naïve B cells, exhibiting a non-classical activation status. Following treatment with anti-CD20, B cells were rapidly depleted in peripheral tissues such as the blood, lymph node and spleen, while depletion in the CNS was delayed. Following treatment there was minimal evidence that anti-CD20 accessed meningeal B cells directly, but rather that depletion was indirect and the result of ongoing turnover of the meningeal population and elimination of the peripheral pool from which it is sustained. Depleting B cells from the CNS resulted in significantly less demyelination and T cell accumulation within meningeal clusters. This suggests that B cells may be required to help with T cell reactivation within the meninges, and that depletion of B cells over time prevents ongoing local pathology. Collectively, this thesis elucidates the phenotype of B cells within the inflamed CNS of anti-myelin autoimmunity, supporting a role for their involvement in disease pathogenesis. By selectively targeting pathogenic populations of B cells this will help minimize the adverse effects that exist with current complete B cell depletion therapies.","abstract_has_math":false,"creators":["Tesfagiorgis, Yodit"],"institution":"The University of Western Ontario","degree_name":"Ph D","degree_level":null,"degree_discipline":"Microbiology and Immunology","degree_department":null,"school":null,"contributors":[],"advisors":["Kerfoot, Steve M."],"committee_chairs":[],"committee_members":[],"year":2021,"date_issued":"2021-01-12","date_published":"2021-01-12","updated_at":"2026-07-27T21:56:05Z","subjects":["Multiple Sclerosis","EAE","autoimmunity","inflammation","B cells","T cells","CNS","CD20"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/30822","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Kerfoot, Steve M."]},{"key":"dc:creator","label":"Author","values":["Tesfagiorgis, Yodit"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T18:45:59Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T18:45:59Z"]},{"key":"dc:date.issued","label":"Date","values":["2021-01-12"]},{"key":"dc:publisher","label":"Institution","values":["The University of Western Ontario"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Microbiology and Immunology"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph D"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Multiple Sclerosis","EAE","autoimmunity","inflammation","B cells","T cells","CNS","CD20"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_ca"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/30822"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["B cell depleting therapies have been effective in the treatment of Multiple Sclerosis (MS), yet to date little is known about how B cells promote disease pathogenesis. B cells can be found invading the meninges around the brain and spinal cord in MS, where they cluster in association with T cells. These meningeal B cells clusters are often adjacent to demyelinating lesions suggesting this may be a site where B cells are exerting their pathogenic effects. The purpose of this thesis was to understand the contribution of meningeal B cells to central nervous system (CNS) autoimmunity, by characterizing their phenotype and determining their susceptibility to B cell depletion. Using an animal model of MS, immunofluorescence analysis, flow cytometry, or single-cell sequencing analysis was used to analyze B cells within the inflamed CNS. Interestingly, while anti-myelin T cells were readily identified in the inflamed CNS, anti-myelin B cells were excluded from this site. Non-specific B cells within the CNS were phenotypically unique from naïve B cells, exhibiting a non-classical activation status. Following treatment with anti-CD20, B cells were rapidly depleted in peripheral tissues such as the blood, lymph node and spleen, while depletion in the CNS was delayed. Following treatment there was minimal evidence that anti-CD20 accessed meningeal B cells directly, but rather that depletion was indirect and the result of ongoing turnover of the meningeal population and elimination of the peripheral pool from which it is sustained. Depleting B cells from the CNS resulted in significantly less demyelination and T cell accumulation within meningeal clusters. This suggests that B cells may be required to help with T cell reactivation within the meninges, and that depletion of B cells over time prevents ongoing local pathology. Collectively, this thesis elucidates the phenotype of B cells within the inflamed CNS of anti-myelin autoimmunity, supporting a role for their involvement in disease pathogenesis. By selectively targeting pathogenic populations of B cells this will help minimize the adverse effects that exist with current complete B cell depletion therapies."]},{"key":"dc:title","label":"Title","values":["Meningeal B cells in central nervous system autoimmunity: Their phenotype and susceptibility to therapeutic depletion"]}]}],"canonical_facts":{"dc:contributor.advisor":["Kerfoot, Steve M."],"dc:creator":["Tesfagiorgis, Yodit"],"dc:date.accessioned":["2025-07-10T18:45:59Z"],"dc:date.available":["2025-07-10T18:45:59Z"],"dc:date.issued":["2021-01-12"],"dc:description":["The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."],"dc:description.abstract":["B cell depleting therapies have been effective in the treatment of Multiple Sclerosis (MS), yet to date little is known about how B cells promote disease pathogenesis. B cells can be found invading the meninges around the brain and spinal cord in MS, where they cluster in association with T cells. These meningeal B cells clusters are often adjacent to demyelinating lesions suggesting this may be a site where B cells are exerting their pathogenic effects. The purpose of this thesis was to understand the contribution of meningeal B cells to central nervous system (CNS) autoimmunity, by characterizing their phenotype and determining their susceptibility to B cell depletion. Using an animal model of MS, immunofluorescence analysis, flow cytometry, or single-cell sequencing analysis was used to analyze B cells within the inflamed CNS. Interestingly, while anti-myelin T cells were readily identified in the inflamed CNS, anti-myelin B cells were excluded from this site. Non-specific B cells within the CNS were phenotypically unique from naïve B cells, exhibiting a non-classical activation status. Following treatment with anti-CD20, B cells were rapidly depleted in peripheral tissues such as the blood, lymph node and spleen, while depletion in the CNS was delayed. Following treatment there was minimal evidence that anti-CD20 accessed meningeal B cells directly, but rather that depletion was indirect and the result of ongoing turnover of the meningeal population and elimination of the peripheral pool from which it is sustained. Depleting B cells from the CNS resulted in significantly less demyelination and T cell accumulation within meningeal clusters. This suggests that B cells may be required to help with T cell reactivation within the meninges, and that depletion of B cells over time prevents ongoing local pathology. Collectively, this thesis elucidates the phenotype of B cells within the inflamed CNS of anti-myelin autoimmunity, supporting a role for their involvement in disease pathogenesis. By selectively targeting pathogenic populations of B cells this will help minimize the adverse effects that exist with current complete B cell depletion therapies."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/30822"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["Multiple Sclerosis","EAE","autoimmunity","inflammation","B cells","T cells","CNS","CD20"],"dc:title":["Meningeal B cells in central nervous system autoimmunity: Their phenotype and susceptibility to therapeutic depletion"],"dc:type":["thesis"],"thesis:degree_discipline":["Microbiology and Immunology"],"thesis:degree_name":["Ph D"]},"updated_at":"2026-07-27T21:56:05Z"}