Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help
To reconcile conflicting reports on the role of CD40 signaling in germinal center (GC) formation, we examined the earliest stages of murine GC B cell differentiation. Peri-follicular GC precursors first expressed intermediate levels of BCL6 while co-expressing the transcription factors RelB and IRF4...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/19552 |
| _version_ | 1811181051173666816 |
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| author | Ting-ting Zhang David G Gonzalez Christine M Cote Steven M Kerfoot Shaoli Deng Yuqing Cheng Masaki Magari Ann M Haberman |
| author_facet | Ting-ting Zhang David G Gonzalez Christine M Cote Steven M Kerfoot Shaoli Deng Yuqing Cheng Masaki Magari Ann M Haberman |
| author_sort | Ting-ting Zhang |
| collection | DOAJ |
| description | To reconcile conflicting reports on the role of CD40 signaling in germinal center (GC) formation, we examined the earliest stages of murine GC B cell differentiation. Peri-follicular GC precursors first expressed intermediate levels of BCL6 while co-expressing the transcription factors RelB and IRF4, the latter known to repress Bcl6 transcription. Transition of GC precursors to the BCL6hi follicular state was associated with cell division, although the number of required cell divisions was immunogen dose dependent. Potentiating T cell help or CD40 signaling in these GC precursors actively repressed GC B cell maturation and diverted their fate towards plasmablast differentiation, whereas depletion of CD4+ T cells promoted this initial transition. Thus while CD40 signaling in B cells is necessary to generate the immediate precursors of GC B cells, transition to the BCL6hi follicular state is promoted by a regional and transient diminution of T cell help. |
| first_indexed | 2024-04-11T09:13:08Z |
| format | Article |
| id | doaj.art-c5cb863a4c5d4283a8eceeaf7dee418c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:13:08Z |
| publishDate | 2017-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c5cb863a4c5d4283a8eceeaf7dee418c2022-12-22T04:32:26ZengeLife Sciences Publications LtdeLife2050-084X2017-05-01610.7554/eLife.19552Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell helpTing-ting Zhang0https://orcid.org/0000-0002-7868-9624David G Gonzalez1Christine M Cote2Steven M Kerfoot3Shaoli Deng4Yuqing Cheng5Masaki Magari6Ann M Haberman7https://orcid.org/0000-0001-5168-8229Department of Laboratory Medicine, Yale University School of Medicine, New Haven, United States; Department of Immunobiology, Yale School of Medicine, New Haven, United StatesDepartment of Laboratory Medicine, Yale University School of Medicine, New Haven, United States; Department of Immunobiology, Yale School of Medicine, New Haven, United StatesDepartment of Immunobiology, Yale School of Medicine, New Haven, United StatesDepartment of Microbiology and Immunology, Western University, London, CanadaThird Military Medical University, Chongqing, ChinaNanjing Normal University, Nanjing, ChinaDepartment of Medical Bioengineering, Okayama University, Okayama, JapanDepartment of Laboratory Medicine, Yale University School of Medicine, New Haven, United States; Department of Immunobiology, Yale School of Medicine, New Haven, United StatesTo reconcile conflicting reports on the role of CD40 signaling in germinal center (GC) formation, we examined the earliest stages of murine GC B cell differentiation. Peri-follicular GC precursors first expressed intermediate levels of BCL6 while co-expressing the transcription factors RelB and IRF4, the latter known to repress Bcl6 transcription. Transition of GC precursors to the BCL6hi follicular state was associated with cell division, although the number of required cell divisions was immunogen dose dependent. Potentiating T cell help or CD40 signaling in these GC precursors actively repressed GC B cell maturation and diverted their fate towards plasmablast differentiation, whereas depletion of CD4+ T cells promoted this initial transition. Thus while CD40 signaling in B cells is necessary to generate the immediate precursors of GC B cells, transition to the BCL6hi follicular state is promoted by a regional and transient diminution of T cell help.https://elifesciences.org/articles/19552germinal centerGC precursortranscription factorCD40plasmablastT cell help |
| spellingShingle | Ting-ting Zhang David G Gonzalez Christine M Cote Steven M Kerfoot Shaoli Deng Yuqing Cheng Masaki Magari Ann M Haberman Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help eLife germinal center GC precursor transcription factor CD40 plasmablast T cell help |
| title | Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help |
| title_full | Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help |
| title_fullStr | Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help |
| title_full_unstemmed | Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help |
| title_short | Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help |
| title_sort | germinal center b cell development has distinctly regulated stages completed by disengagement from t cell help |
| topic | germinal center GC precursor transcription factor CD40 plasmablast T cell help |
| url | https://elifesciences.org/articles/19552 |
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