Vagus nerve stimulation modulates distinct acetylcholine receptors on B cells and limits the germinal center response
Acetylcholine is produced in the spleen in response to vagus nerve activation; however, the effects on antibody production have been largely unexplored. Here, we use a chronic vagus nerve stimulation (VNS) mouse model to study the effect of VNS on T-dependent B cell responses. We observed lower titers of high-affinity IgG and fewer antigen-specific germinal center (GC) B cells. GC B cells from chronic VNS mice exhibited altered mRNA and protein expression suggesting increased apoptosis and impaired plasma cell differentiation. Follicular dendritic cell (FDC) cluster dispersal and altered gene expression suggested poor function. The absence of acetylcholine-producing CD4+ T cells diminished these alterations. In vitro studies revealed that α7 and α9 nicotinic acetylcholine receptors (nAChRs) directly regulated B cell production of TNF, a cytokine crucial to FDC clustering. α4 nAChR inhibited coligation of CD19 to the B cell receptor, presumably decreasing B cell survival. Thus, VNS-induced GC impairment can be attributed to distinct effects of nAChRs on B cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Science advances - 10(2024), 17 vom: 26. Apr., Seite eadn3760 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kurata-Sato, Izumi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.04.2024 Date Revised 28.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1126/sciadv.adn3760 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM371581850 |
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| 245 | 1 | 0 | |a Vagus nerve stimulation modulates distinct acetylcholine receptors on B cells and limits the germinal center response |
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| 520 | |a Acetylcholine is produced in the spleen in response to vagus nerve activation; however, the effects on antibody production have been largely unexplored. Here, we use a chronic vagus nerve stimulation (VNS) mouse model to study the effect of VNS on T-dependent B cell responses. We observed lower titers of high-affinity IgG and fewer antigen-specific germinal center (GC) B cells. GC B cells from chronic VNS mice exhibited altered mRNA and protein expression suggesting increased apoptosis and impaired plasma cell differentiation. Follicular dendritic cell (FDC) cluster dispersal and altered gene expression suggested poor function. The absence of acetylcholine-producing CD4+ T cells diminished these alterations. In vitro studies revealed that α7 and α9 nicotinic acetylcholine receptors (nAChRs) directly regulated B cell production of TNF, a cytokine crucial to FDC clustering. α4 nAChR inhibited coligation of CD19 to the B cell receptor, presumably decreasing B cell survival. Thus, VNS-induced GC impairment can be attributed to distinct effects of nAChRs on B cells | ||
| 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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| 700 | 1 | |a Mughrabi, Ibrahim T |e verfasserin |4 aut | |
| 700 | 1 | |a Rana, Minakshi |e verfasserin |4 aut | |
| 700 | 1 | |a Gerber, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Abed, Yousef |e verfasserin |4 aut | |
| 700 | 1 | |a Sherry, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Zanos, Stavros |e verfasserin |4 aut | |
| 700 | 1 | |a Diamond, Betty |e verfasserin |4 aut | |
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