Marginal zone SIGN-R1(+) macrophages are essential for the maturation of germinal centre B cells in the spleen
<p>The germinal centre (GC) response is an essential component of adaptive immunity, crucial for the generation of high-affinity antibodies, long-lived memory and plasma cells and is the basis for most current vaccines. While the dynamics of cognate B and T lymphocytes during the GC response a...
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| Format: | Thesis |
| Language: | English |
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2021
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| _version_ | 1817932048770269184 |
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| author | Pirgova, GT |
| author2 | Arnon, TI |
| author_facet | Arnon, TI Pirgova, GT |
| author_sort | Pirgova, GT |
| collection | OXFORD |
| description | <p>The germinal centre (GC) response is an essential component of adaptive immunity, crucial for the generation of high-affinity antibodies, long-lived memory and plasma cells and is the basis for most current vaccines. While the dynamics of cognate B and T lymphocytes during the GC response are extensively studied, the roles of resident tissue macrophages in this process are less well understood, particularly in the spleen. A unique compartment to the spleen, called the marginal (MZ), is known to be important for adaptive immunity and harbours at least two distinct MZ-resident macrophage subsets. Both MZ macrophage populations are essential for capturing and preventing systemic dissemination of pathogens. However, their individual functions and potential role in adaptive immunity are not established. </p>
<p>Here we used pharmacologic and genetic approaches to deplete SIGN-R1+ MZ macrophages and showed that these cells were specifically required for the optimal development of germinal centre responses in the spleen. SIGN-R1+ macrophages were dispensable for the initial GC establishment but were required for optimal maintenance of the response. The GC defect could be partially corrected by boosting T follicular helper (Tfh) cell responses or by inducing Tfh help prior to macrophage ablation. Furthermore, in the absence of SIGN-R1+ macrophages, 33D1+ DCs, a key population involved in Tfh priming, was displaced from the interfollicular regions to the MZ. Reconstituting the SIGN-R1+ subset restored DC positioning and rescued the GC phenotype. This work advances our understanding of how the splenic marginal zone regulates adaptive immunity, highlights the functional diversification of MZ macrophages, and provides the first genetic mouse model allowing for the specific depletion and modification of SIGN-R1+ cells.</p>
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| first_indexed | 2024-03-06T19:12:25Z |
| format | Thesis |
| id | oxford-uuid:1736899e-cfc4-47d2-a5d0-cb544365ee5a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:31:43Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | oxford-uuid:1736899e-cfc4-47d2-a5d0-cb544365ee5a2024-12-01T15:05:54ZMarginal zone SIGN-R1(+) macrophages are essential for the maturation of germinal centre B cells in the spleenThesishttp://purl.org/coar/resource_type/c_db06uuid:1736899e-cfc4-47d2-a5d0-cb544365ee5aImmunologyEnglishHyrax Deposit2021Pirgova, GTArnon, TIDustin, ML<p>The germinal centre (GC) response is an essential component of adaptive immunity, crucial for the generation of high-affinity antibodies, long-lived memory and plasma cells and is the basis for most current vaccines. While the dynamics of cognate B and T lymphocytes during the GC response are extensively studied, the roles of resident tissue macrophages in this process are less well understood, particularly in the spleen. A unique compartment to the spleen, called the marginal (MZ), is known to be important for adaptive immunity and harbours at least two distinct MZ-resident macrophage subsets. Both MZ macrophage populations are essential for capturing and preventing systemic dissemination of pathogens. However, their individual functions and potential role in adaptive immunity are not established. </p> <p>Here we used pharmacologic and genetic approaches to deplete SIGN-R1+ MZ macrophages and showed that these cells were specifically required for the optimal development of germinal centre responses in the spleen. SIGN-R1+ macrophages were dispensable for the initial GC establishment but were required for optimal maintenance of the response. The GC defect could be partially corrected by boosting T follicular helper (Tfh) cell responses or by inducing Tfh help prior to macrophage ablation. Furthermore, in the absence of SIGN-R1+ macrophages, 33D1+ DCs, a key population involved in Tfh priming, was displaced from the interfollicular regions to the MZ. Reconstituting the SIGN-R1+ subset restored DC positioning and rescued the GC phenotype. This work advances our understanding of how the splenic marginal zone regulates adaptive immunity, highlights the functional diversification of MZ macrophages, and provides the first genetic mouse model allowing for the specific depletion and modification of SIGN-R1+ cells.</p> |
| spellingShingle | Immunology Pirgova, GT Marginal zone SIGN-R1(+) macrophages are essential for the maturation of germinal centre B cells in the spleen |
| title | Marginal zone SIGN-R1(+) macrophages are essential for the maturation of germinal centre B cells in the spleen |
| title_full | Marginal zone SIGN-R1(+) macrophages are essential for the maturation of germinal centre B cells in the spleen |
| title_fullStr | Marginal zone SIGN-R1(+) macrophages are essential for the maturation of germinal centre B cells in the spleen |
| title_full_unstemmed | Marginal zone SIGN-R1(+) macrophages are essential for the maturation of germinal centre B cells in the spleen |
| title_short | Marginal zone SIGN-R1(+) macrophages are essential for the maturation of germinal centre B cells in the spleen |
| title_sort | marginal zone sign r1 macrophages are essential for the maturation of germinal centre b cells in the spleen |
| topic | Immunology |
| work_keys_str_mv | AT pirgovagt marginalzonesignr1macrophagesareessentialforthematurationofgerminalcentrebcellsinthespleen |