Evolution of antigen-specific follicular helper T cell transcription from effector function to memory
Understanding how follicular helper T cells (TFH) regulate the specialization, maturation, and differentiation of adaptive B cell immunity is crucial for developing durable high-affinity immune protection. Using indexed single-cell molecular strategies, we reveal a skewed intraclonal assortment of higher-affinity T cell receptors and the distinct molecular programming of the localized TFH compartment compared with emigrant conventional effector TH cells. We find a temporal shift in B cell receptor class switch, which permits identification of inflammatory and anti-inflammatory modules of transcriptional programming that subspecialize TFH function before and during the germinal center (GC) reaction. Late collapse of this local primary GC reaction reveals a persistent post-GC TFH population that discloses a putative memory TFH program. These studies define subspecialized antigen-specific TFH transcriptional programs that progressively change with antibody class-specific evolution of high-affinity B cell immunity and a memory TFH transcriptional program that emerges upon local GC resolution.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Science immunology - 7(2022), 76 vom: 14. Okt., Seite eabm2084 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Robinson, Amanda M [VerfasserIn] |
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| Links: |
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| Themen: |
Antigens |
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| Anmerkungen: |
Date Completed 11.10.2022 Date Revised 15.04.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1126/sciimmunol.abm2084 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM347216579 |
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| 500 | |a Date Revised 15.04.2023 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Understanding how follicular helper T cells (TFH) regulate the specialization, maturation, and differentiation of adaptive B cell immunity is crucial for developing durable high-affinity immune protection. Using indexed single-cell molecular strategies, we reveal a skewed intraclonal assortment of higher-affinity T cell receptors and the distinct molecular programming of the localized TFH compartment compared with emigrant conventional effector TH cells. We find a temporal shift in B cell receptor class switch, which permits identification of inflammatory and anti-inflammatory modules of transcriptional programming that subspecialize TFH function before and during the germinal center (GC) reaction. Late collapse of this local primary GC reaction reveals a persistent post-GC TFH population that discloses a putative memory TFH program. These studies define subspecialized antigen-specific TFH transcriptional programs that progressively change with antibody class-specific evolution of high-affinity B cell immunity and a memory TFH transcriptional program that emerges upon local GC resolution | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
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| 650 | 7 | |a Immunoglobulin Isotypes |2 NLM | |
| 650 | 7 | |a Receptors, Antigen, B-Cell |2 NLM | |
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| 700 | 1 | |a Shuparski, Andrew G |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Karen B |e verfasserin |4 aut | |
| 700 | 1 | |a McHeyzer-Williams, Louise J |e verfasserin |4 aut | |
| 700 | 1 | |a McHeyzer-Williams, Michael G |e verfasserin |4 aut | |
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