{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/307698"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/307698","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"Investigating the phenotype and function of tissue-resident B cells in mouse and human non-lymphoid organs","abstract":"B lymphocytes play a central role in humoral immunity but also have antibody-independent functions. Studies to date have focused on B cells within blood and secondary lymphoid organs. This thesis sought to address the question of whether B cells reside in non-lymphoid organs (NLOs), and to determine their phenotype and function. Using intravenous labelling and parabiosis, we identified a population of bona-fide self-renewing, tissue-resident B cells, represented mainly by innate-like CD5+ B-1 cells, across murine NLOs, including lung, liver, kidney and bladder. The size and phenotype of this tissue-resident B-cell subset was influenced by genetic background, age and the microbiome, with an expanded population evident in pet-store mice. Extravascular B cells had less diverse Igh repertoire with fewer N-additions compared to blood, suggesting their prenatal origin. Seeding of these B cells into NLOs was independent of their antigen specificity. Using strains of genetically modified mice with higher (PI3Kδ E1020K-B, Siglec-G-/-) or lower (μMT-) numbers of tissue-resident B cells in NLOs, we tested the function of these cells in the context of urinary tract infection. The number of tissue-resident B cells inversely correlated with bacterial clearance suggesting that B cells negatively regulate anti-microbial responses. Tissue-resident B cells were spatially co-localised with macrophages and had a profound effect on macrophage polarisation, promoting an anti-inflammatory M2 phenotype, an effect at least partially driven via interleukin (IL)-10. Finally, in human NLOs we found a similar enrichment for non-naïve less diverse B cells when compared to blood and spleen, with indices for innate-like and regulatory phenotype. In conclusion, these data identify a critical role for tissue-resident B cells in modulating organ immunity, determining inflammatory 'set-point' of resident and recruited myeloid cells, with important clinical implications.","abstract_html":"B lymphocytes play a central role in humoral immunity but also have antibody-independent functions. Studies to date have focused on B cells within blood and secondary lymphoid organs. This thesis sought to address the question of whether B cells reside in non-lymphoid organs (NLOs), and to determine their phenotype and function. Using intravenous labelling and parabiosis, we identified a population of bona-fide self-renewing, tissue-resident B cells, represented mainly by innate-like CD5+ B-1 cells, across murine NLOs, including lung, liver, kidney and bladder. The size and phenotype of this tissue-resident B-cell subset was influenced by genetic background, age and the microbiome, with an expanded population evident in pet-store mice. Extravascular B cells had less diverse Igh repertoire with fewer N-additions compared to blood, suggesting their prenatal origin. Seeding of these B cells into NLOs was independent of their antigen specificity. Using strains of genetically modified mice with higher (PI3Kδ E1020K-B, Siglec-G-/-) or lower (μMT-) numbers of tissue-resident B cells in NLOs, we tested the function of these cells in the context of urinary tract infection. The number of tissue-resident B cells inversely correlated with bacterial clearance suggesting that B cells negatively regulate anti-microbial responses. Tissue-resident B cells were spatially co-localised with macrophages and had a profound effect on macrophage polarisation, promoting an anti-inflammatory M2 phenotype, an effect at least partially driven via interleukin (IL)-10. Finally, in human NLOs we found a similar enrichment for non-naïve less diverse B cells when compared to blood and spleen, with indices for innate-like and regulatory phenotype. In conclusion, these data identify a critical role for tissue-resident B cells in modulating organ immunity, determining inflammatory 'set-point' of resident and recruited myeloid cells, with important clinical implications.","abstract_has_math":false,"creators":["Suchanek, Ondrej"],"institution":"University of Cambridge","degree_name":"Doctor of Philosophy (PhD)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Clatworthy, Menna"],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-03-27","date_published":"2020-03-27","updated_at":"2026-07-22T22:24:08Z","subjects":["B lymphocyte","tissue-resident","macrophage","polarisation","kidney"],"languages":["eng"],"rights":[],"rights_urls":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/a8759ba6-44d1-4624-bee9-f0a6bea31a16/download","https://www.rioxx.net/licenses/all-rights-reserved/"],"identifier_entries":[{"key":"dc:creator.authoridentifier","label":"Author Identifier","values":["0000000310485251","0000000233409828"],"render_values":[{"text":"0000-0003-1048-5251","href":"https://orcid.org/0000-0003-1048-5251","code":true},{"text":"0000-0002-3340-9828","href":"https://orcid.org/0000-0002-3340-9828","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.17863/CAM.54791","outbound_label":"DOI","outbound_source":"dc:identifier.doi"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Clatworthy, Menna"]},{"key":"dc:contributor.sponsor","label":"Sponsor","values":["Wellcome Trust"]},{"key":"dc:creator","label":"Author","values":["Suchanek, Ondrej"]},{"key":"dc:creator.authoridentifier","label":"Author Identifier","values":["0000000310485251","0000000233409828"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2020-03-27"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cambridge"]},{"key":"dc:relation.isreferencedby.uri","label":"Dc Relation Isreferencedby URI","values":["https://www.repository.cam.ac.uk/handle/1810/307698"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["B lymphocyte","tissue-resident","macrophage","polarisation","kidney"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/a8759ba6-44d1-4624-bee9-f0a6bea31a16/download","https://www.rioxx.net/licenses/all-rights-reserved/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.17863/CAM.54791"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/848c79d3-53c7-45c2-8f2b-a1fef8b33c17/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["B lymphocytes play a central role in humoral immunity but also have antibody-independent functions. Studies to date have focused on B cells within blood and secondary lymphoid organs. This thesis sought to address the question of whether B cells reside in non-lymphoid organs (NLOs), and to determine their phenotype and function. Using intravenous labelling and parabiosis, we identified a population of bona-fide self-renewing, tissue-resident B cells, represented mainly by innate-like CD5+ B-1 cells, across murine NLOs, including lung, liver, kidney and bladder. The size and phenotype of this tissue-resident B-cell subset was influenced by genetic background, age and the microbiome, with an expanded population evident in pet-store mice. Extravascular B cells had less diverse Igh repertoire with fewer N-additions compared to blood, suggesting their prenatal origin. Seeding of these B cells into NLOs was independent of their antigen specificity. Using strains of genetically modified mice with higher (PI3Kδ E1020K-B, Siglec-G-/-) or lower (μMT-) numbers of tissue-resident B cells in NLOs, we tested the function of these cells in the context of urinary tract infection. The number of tissue-resident B cells inversely correlated with bacterial clearance suggesting that B cells negatively regulate anti-microbial responses. Tissue-resident B cells were spatially co-localised with macrophages and had a profound effect on macrophage polarisation, promoting an anti-inflammatory M2 phenotype, an effect at least partially driven via interleukin (IL)-10. Finally, in human NLOs we found a similar enrichment for non-naïve less diverse B cells when compared to blood and spleen, with indices for innate-like and regulatory phenotype. In conclusion, these data identify a critical role for tissue-resident B cells in modulating organ immunity, determining inflammatory 'set-point' of resident and recruited myeloid cells, with important clinical implications."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["4eeb0a6bf437acc323e84bca301f9c8e","353adac0d1ebdfd65ab16480263c3c87"]},{"key":"dc:title","label":"Title","values":["Investigating the phenotype and function of tissue-resident B cells in mouse and human non-lymphoid organs"]}]}],"canonical_facts":{"dc:contributor.advisor":["Clatworthy, Menna"],"dc:contributor.sponsor":["Wellcome Trust"],"dc:creator":["Suchanek, Ondrej"],"dc:creator.authoridentifier":["0000000310485251","0000000233409828"],"dc:date.issued":["2020-03-27"],"dc:description.abstract":["B lymphocytes play a central role in humoral immunity but also have antibody-independent functions. Studies to date have focused on B cells within blood and secondary lymphoid organs. This thesis sought to address the question of whether B cells reside in non-lymphoid organs (NLOs), and to determine their phenotype and function. Using intravenous labelling and parabiosis, we identified a population of bona-fide self-renewing, tissue-resident B cells, represented mainly by innate-like CD5+ B-1 cells, across murine NLOs, including lung, liver, kidney and bladder. The size and phenotype of this tissue-resident B-cell subset was influenced by genetic background, age and the microbiome, with an expanded population evident in pet-store mice. Extravascular B cells had less diverse Igh repertoire with fewer N-additions compared to blood, suggesting their prenatal origin. Seeding of these B cells into NLOs was independent of their antigen specificity. Using strains of genetically modified mice with higher (PI3Kδ E1020K-B, Siglec-G-/-) or lower (μMT-) numbers of tissue-resident B cells in NLOs, we tested the function of these cells in the context of urinary tract infection. The number of tissue-resident B cells inversely correlated with bacterial clearance suggesting that B cells negatively regulate anti-microbial responses. Tissue-resident B cells were spatially co-localised with macrophages and had a profound effect on macrophage polarisation, promoting an anti-inflammatory M2 phenotype, an effect at least partially driven via interleukin (IL)-10. Finally, in human NLOs we found a similar enrichment for non-naïve less diverse B cells when compared to blood and spleen, with indices for innate-like and regulatory phenotype. In conclusion, these data identify a critical role for tissue-resident B cells in modulating organ immunity, determining inflammatory 'set-point' of resident and recruited myeloid cells, with important clinical implications."],"dc:format.checksum.md5":["4eeb0a6bf437acc323e84bca301f9c8e","353adac0d1ebdfd65ab16480263c3c87"],"dc:identifier.doi":["10.17863/CAM.54791"],"dc:identifier.uri":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/848c79d3-53c7-45c2-8f2b-a1fef8b33c17/download"],"dc:language":["eng"],"dc:publisher.institution":["University of Cambridge"],"dc:relation.isreferencedby.uri":["https://www.repository.cam.ac.uk/handle/1810/307698"],"dc:rights":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/a8759ba6-44d1-4624-bee9-f0a6bea31a16/download","https://www.rioxx.net/licenses/all-rights-reserved/"],"dc:subject":["B lymphocyte","tissue-resident","macrophage","polarisation","kidney"],"dc:title":["Investigating the phenotype and function of tissue-resident B cells in mouse and human non-lymphoid organs"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral"],"dc:type.qualificationname":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-22T22:24:08Z"}