Marginal zone SIGN-R1+ macrophages are essential for the maturation of germinal centre B cells in the spleen
The mechanisms that regulate germinal center (GC) B cell responses in the spleen are not fully understood. Here we use a combination of pharmacologic and genetic approaches to delete SIGN-R1+ marginal zone (MZ) macrophages and reveal their specific contribution to the regulation of humoral immunity...
| Հիմնական հեղինակներ: | , , , , |
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| Ձևաչափ: | Journal article |
| Լեզու: | English |
| Հրապարակվել է: |
National Academy of Sciences
2020
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| _version_ | 1826306215949369344 |
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| author | Pirgova, G Chauveau, A Maclean, AJ Cyster, JG Arnon, T |
| author_facet | Pirgova, G Chauveau, A Maclean, AJ Cyster, JG Arnon, T |
| author_sort | Pirgova, G |
| collection | OXFORD |
| description | The mechanisms that regulate germinal center (GC) B cell responses in the spleen are not fully understood. Here we use a combination of pharmacologic and genetic approaches to delete SIGN-R1+ marginal zone (MZ) macrophages and reveal their specific contribution to the regulation of humoral immunity in the spleen. We find that while SIGN-R1+ macrophages were not essential for initial activation of B cells, they were required for maturation of the response and development of GC B cells. These defects could be corrected when follicular helper T (Tfh) cells were induced before macrophage ablation or when Tfh responses were enhanced. Moreover, we show that in the absence of SIGN-R1+ macrophages, DCIR2+ dendritic cells (DCs), which play a key role in priming Tfh responses, were unable to cluster to the interfollicular regions of the spleen and were instead displaced to the MZ. Restoring SIGN-R1+ macrophages to the spleen corrected positioning of DCIR2+ DCs and rescued the GC B cell response. Our study reveals a previously unappreciated role for SIGN-R1+ macrophages in regulation of the GC reaction and highlights the functional specification of macrophage subsets in the MZ compartment. |
| first_indexed | 2024-03-07T06:44:34Z |
| format | Journal article |
| id | oxford-uuid:fa6de7a2-3943-482a-afb6-5be205495a11 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:44:34Z |
| publishDate | 2020 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:fa6de7a2-3943-482a-afb6-5be205495a112022-03-27T13:05:48ZMarginal zone SIGN-R1+ macrophages are essential for the maturation of germinal centre B cells in the spleenJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fa6de7a2-3943-482a-afb6-5be205495a11EnglishSymplectic ElementsNational Academy of Sciences2020Pirgova, GChauveau, AMaclean, AJCyster, JGArnon, TThe mechanisms that regulate germinal center (GC) B cell responses in the spleen are not fully understood. Here we use a combination of pharmacologic and genetic approaches to delete SIGN-R1+ marginal zone (MZ) macrophages and reveal their specific contribution to the regulation of humoral immunity in the spleen. We find that while SIGN-R1+ macrophages were not essential for initial activation of B cells, they were required for maturation of the response and development of GC B cells. These defects could be corrected when follicular helper T (Tfh) cells were induced before macrophage ablation or when Tfh responses were enhanced. Moreover, we show that in the absence of SIGN-R1+ macrophages, DCIR2+ dendritic cells (DCs), which play a key role in priming Tfh responses, were unable to cluster to the interfollicular regions of the spleen and were instead displaced to the MZ. Restoring SIGN-R1+ macrophages to the spleen corrected positioning of DCIR2+ DCs and rescued the GC B cell response. Our study reveals a previously unappreciated role for SIGN-R1+ macrophages in regulation of the GC reaction and highlights the functional specification of macrophage subsets in the MZ compartment. |
| spellingShingle | Pirgova, G Chauveau, A Maclean, AJ Cyster, JG Arnon, T 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 |
| work_keys_str_mv | AT pirgovag marginalzonesignr1macrophagesareessentialforthematurationofgerminalcentrebcellsinthespleen AT chauveaua marginalzonesignr1macrophagesareessentialforthematurationofgerminalcentrebcellsinthespleen AT macleanaj marginalzonesignr1macrophagesareessentialforthematurationofgerminalcentrebcellsinthespleen AT cysterjg marginalzonesignr1macrophagesareessentialforthematurationofgerminalcentrebcellsinthespleen AT arnont marginalzonesignr1macrophagesareessentialforthematurationofgerminalcentrebcellsinthespleen |