B Cell Diversification Is Uncoupled from SAP-Mediated Selection Forces in Chronic Germinal Centers within Peyer’s Patches
Summary: Antibodies secreted within the intestinal tract provide protection from the invasion of microbes into the host tissues. Germinal center (GC) formation in lymph nodes and spleen strictly requires SLAM-associated protein (SAP)-mediated T cell functions; however, it is not known whether this m...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-02-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720300474 |
| _version_ | 1828530631305330688 |
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| author | Adi Biram Eitan Winter Alice E. Denton Irina Zaretsky Bareket Dassa Mats Bemark Michelle A. Linterman Gur Yaari Ziv Shulman |
| author_facet | Adi Biram Eitan Winter Alice E. Denton Irina Zaretsky Bareket Dassa Mats Bemark Michelle A. Linterman Gur Yaari Ziv Shulman |
| author_sort | Adi Biram |
| collection | DOAJ |
| description | Summary: Antibodies secreted within the intestinal tract provide protection from the invasion of microbes into the host tissues. Germinal center (GC) formation in lymph nodes and spleen strictly requires SLAM-associated protein (SAP)-mediated T cell functions; however, it is not known whether this mechanism plays a similar role in mucosal-associated lymphoid tissues. Here, we find that in Peyer’s patches (PPs), SAP-mediated T cell help is required for promoting B cell selection in GCs, but not for clonal diversification. PPs of SAP-deficient mice host chronic GCs that are absent in T cell-deficient mice. GC B cells in SAP-deficient mice express AID and Bcl6 and generate plasma cells in proportion to the GC size. Single-cell IgA sequencing analysis reveals that these mice host few diversified clones that were subjected to mild selection forces. These findings demonstrate that T cell-derived help to B cells in PPs includes SAP-dependent and SAP-independent functions. : SAP is required for proper T cell help in germinal centers (GCs). Biram et al. show that SAP-independent GCs are formed within Peyer’s patches. These GCs host highly diversified clones that are subjected to mild selection forces, demonstrating that clonal diversification can be uncoupled from clonal selection in chronic GCs. Keywords: germinal center, antibody, B cells, SAP, T follicular helper cells, Peyer’s patches, clonal diversification, IgA, plasma cells |
| first_indexed | 2024-12-11T22:26:04Z |
| format | Article |
| id | doaj.art-6dc1f77208d54ea8b19bc44966092cbb |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T22:26:04Z |
| publishDate | 2020-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-6dc1f77208d54ea8b19bc44966092cbb2022-12-22T00:48:17ZengElsevierCell Reports2211-12472020-02-0130619101922.e5B Cell Diversification Is Uncoupled from SAP-Mediated Selection Forces in Chronic Germinal Centers within Peyer’s PatchesAdi Biram0Eitan Winter1Alice E. Denton2Irina Zaretsky3Bareket Dassa4Mats Bemark5Michelle A. Linterman6Gur Yaari7Ziv Shulman8Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, IsraelFaculty of Engineering, Bar Ilan University, Ramat Gan 52900, IsraelLaboratory of Lymphocyte Signaling and Development, Babraham Institute, Cambridge CB22 3AT, UKDepartment of Immunology, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Life Science Core Facilities, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg SE-405 30, SwedenLaboratory of Lymphocyte Signaling and Development, Babraham Institute, Cambridge CB22 3AT, UKFaculty of Engineering, Bar Ilan University, Ramat Gan 52900, IsraelDepartment of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel; Corresponding authorSummary: Antibodies secreted within the intestinal tract provide protection from the invasion of microbes into the host tissues. Germinal center (GC) formation in lymph nodes and spleen strictly requires SLAM-associated protein (SAP)-mediated T cell functions; however, it is not known whether this mechanism plays a similar role in mucosal-associated lymphoid tissues. Here, we find that in Peyer’s patches (PPs), SAP-mediated T cell help is required for promoting B cell selection in GCs, but not for clonal diversification. PPs of SAP-deficient mice host chronic GCs that are absent in T cell-deficient mice. GC B cells in SAP-deficient mice express AID and Bcl6 and generate plasma cells in proportion to the GC size. Single-cell IgA sequencing analysis reveals that these mice host few diversified clones that were subjected to mild selection forces. These findings demonstrate that T cell-derived help to B cells in PPs includes SAP-dependent and SAP-independent functions. : SAP is required for proper T cell help in germinal centers (GCs). Biram et al. show that SAP-independent GCs are formed within Peyer’s patches. These GCs host highly diversified clones that are subjected to mild selection forces, demonstrating that clonal diversification can be uncoupled from clonal selection in chronic GCs. Keywords: germinal center, antibody, B cells, SAP, T follicular helper cells, Peyer’s patches, clonal diversification, IgA, plasma cellshttp://www.sciencedirect.com/science/article/pii/S2211124720300474 |
| spellingShingle | Adi Biram Eitan Winter Alice E. Denton Irina Zaretsky Bareket Dassa Mats Bemark Michelle A. Linterman Gur Yaari Ziv Shulman B Cell Diversification Is Uncoupled from SAP-Mediated Selection Forces in Chronic Germinal Centers within Peyer’s Patches Cell Reports |
| title | B Cell Diversification Is Uncoupled from SAP-Mediated Selection Forces in Chronic Germinal Centers within Peyer’s Patches |
| title_full | B Cell Diversification Is Uncoupled from SAP-Mediated Selection Forces in Chronic Germinal Centers within Peyer’s Patches |
| title_fullStr | B Cell Diversification Is Uncoupled from SAP-Mediated Selection Forces in Chronic Germinal Centers within Peyer’s Patches |
| title_full_unstemmed | B Cell Diversification Is Uncoupled from SAP-Mediated Selection Forces in Chronic Germinal Centers within Peyer’s Patches |
| title_short | B Cell Diversification Is Uncoupled from SAP-Mediated Selection Forces in Chronic Germinal Centers within Peyer’s Patches |
| title_sort | b cell diversification is uncoupled from sap mediated selection forces in chronic germinal centers within peyer s patches |
| url | http://www.sciencedirect.com/science/article/pii/S2211124720300474 |
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