Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells
© 2020 Pae et al. During affinity maturation, germinal center (GC) B cells alternate between proliferation and somatic hypermutation in the dark zone (DZ) and affinity-dependent selection in the light zone (LZ). This anatomical segregation imposes that the vigorous proliferation that allows clonal e...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Rockefeller University Press
2022
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| Online Access: | https://hdl.handle.net/1721.1/141292 |
| _version_ | 1826207070454546432 |
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| author | Pae, Juhee Ersching, Jonatan Castro, Tiago BR Schips, Marta Mesin, Luka Allon, Samuel J Ordovas-Montanes, Jose Mlynarczyk, Coraline Melnick, Ari Efeyan, Alejo Shalek, Alex K Meyer-Hermann, Michael Victora, Gabriel D |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Pae, Juhee Ersching, Jonatan Castro, Tiago BR Schips, Marta Mesin, Luka Allon, Samuel J Ordovas-Montanes, Jose Mlynarczyk, Coraline Melnick, Ari Efeyan, Alejo Shalek, Alex K Meyer-Hermann, Michael Victora, Gabriel D |
| author_sort | Pae, Juhee |
| collection | MIT |
| description | © 2020 Pae et al. During affinity maturation, germinal center (GC) B cells alternate between proliferation and somatic hypermutation in the dark zone (DZ) and affinity-dependent selection in the light zone (LZ). This anatomical segregation imposes that the vigorous proliferation that allows clonal expansion of positively selected GC B cells takes place ostensibly in the absence of the signals that triggered selection in the LZ, as if by "inertia."We find that such inertial cycles specifically require the cell cycle regulator cyclin D3. Cyclin D3 dose-dependently controls the extent to which B cells proliferate in the DZ and is essential for effective clonal expansion of GC B cells in response to strong T follicular helper (Tfh) cell help. Introduction into the Ccnd3 gene of a Burkitt lymphoma-associated gain-of-function mutation (T283A) leads to larger GCs with increased DZ proliferation and, in older mice, clonal B cell lymphoproliferation, suggesting that the DZ inertial cell cycle program can be coopted by B cells undergoing malignant transformation. |
| first_indexed | 2024-09-23T13:43:02Z |
| format | Article |
| id | mit-1721.1/141292 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:43:02Z |
| publishDate | 2022 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | mit-1721.1/1412922024-03-20T18:54:32Z Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells Pae, Juhee Ersching, Jonatan Castro, Tiago BR Schips, Marta Mesin, Luka Allon, Samuel J Ordovas-Montanes, Jose Mlynarczyk, Coraline Melnick, Ari Efeyan, Alejo Shalek, Alex K Meyer-Hermann, Michael Victora, Gabriel D Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Chemistry Koch Institute for Integrative Cancer Research at MIT Ragon Institute of MGH, MIT and Harvard © 2020 Pae et al. During affinity maturation, germinal center (GC) B cells alternate between proliferation and somatic hypermutation in the dark zone (DZ) and affinity-dependent selection in the light zone (LZ). This anatomical segregation imposes that the vigorous proliferation that allows clonal expansion of positively selected GC B cells takes place ostensibly in the absence of the signals that triggered selection in the LZ, as if by "inertia."We find that such inertial cycles specifically require the cell cycle regulator cyclin D3. Cyclin D3 dose-dependently controls the extent to which B cells proliferate in the DZ and is essential for effective clonal expansion of GC B cells in response to strong T follicular helper (Tfh) cell help. Introduction into the Ccnd3 gene of a Burkitt lymphoma-associated gain-of-function mutation (T283A) leads to larger GCs with increased DZ proliferation and, in older mice, clonal B cell lymphoproliferation, suggesting that the DZ inertial cell cycle program can be coopted by B cells undergoing malignant transformation. 2022-03-18T15:04:35Z 2022-03-18T15:04:35Z 2021 2022-03-18T15:00:40Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/141292 Pae, Juhee, Ersching, Jonatan, Castro, Tiago BR, Schips, Marta, Mesin, Luka et al. 2021. "Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells." The Journal of Experimental Medicine, 218 (4). en 10.1084/JEM.20201699 The Journal of Experimental Medicine Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Rockefeller University Press Rockefeller University Press |
| spellingShingle | Pae, Juhee Ersching, Jonatan Castro, Tiago BR Schips, Marta Mesin, Luka Allon, Samuel J Ordovas-Montanes, Jose Mlynarczyk, Coraline Melnick, Ari Efeyan, Alejo Shalek, Alex K Meyer-Hermann, Michael Victora, Gabriel D Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells |
| title | Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells |
| title_full | Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells |
| title_fullStr | Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells |
| title_full_unstemmed | Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells |
| title_short | Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells |
| title_sort | cyclin d3 drives inertial cell cycling in dark zone germinal center b cells |
| url | https://hdl.handle.net/1721.1/141292 |
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