Cargando…
Type I Interferons Promote Germinal Centers Through B Cell Intrinsic Signaling and Dendritic Cell Dependent Th1 and Tfh Cell Lineages
Type I interferons (IFNs) are essential for antiviral immunity, appear to represent a key component of mRNA vaccine-adjuvanticity, and correlate with severity of systemic autoimmune disease. Relevant to all, type I IFNs can enhance germinal center (GC) B cell responses but underlying signaling pathw...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326081/ https://www.ncbi.nlm.nih.gov/pubmed/35911733 http://dx.doi.org/10.3389/fimmu.2022.932388 |
_version_ | 1784757197901660160 |
---|---|
author | Dahlgren, Madelene W. Plumb, Adam W. Niss, Kristoffer Lahl, Katharina Brunak, Søren Johansson-Lindbom, Bengt |
author_facet | Dahlgren, Madelene W. Plumb, Adam W. Niss, Kristoffer Lahl, Katharina Brunak, Søren Johansson-Lindbom, Bengt |
author_sort | Dahlgren, Madelene W. |
collection | PubMed |
description | Type I interferons (IFNs) are essential for antiviral immunity, appear to represent a key component of mRNA vaccine-adjuvanticity, and correlate with severity of systemic autoimmune disease. Relevant to all, type I IFNs can enhance germinal center (GC) B cell responses but underlying signaling pathways are incompletely understood. Here, we demonstrate that a succinct type I IFN response promotes GC formation and associated IgG subclass distribution primarily through signaling in cDCs and B cells. Type I IFN signaling in cDCs, distinct from cDC1, stimulates development of separable Tfh and Th1 cell subsets. However, Th cell-derived IFN-γ induces T-bet expression and IgG2c isotype switching in B cells prior to this bifurcation and has no evident effects once GCs and bona fide Tfh cells developed. This pathway acts in synergy with early B cell-intrinsic type I IFN signaling, which reinforces T-bet expression in B cells and leads to a selective amplification of the IgG2c(+) GC B cell response. Despite the strong Th1 polarizing effect of type I IFNs, the Tfh cell subset develops into IL-4 producing cells that control the overall magnitude of the GCs and promote generation of IgG1(+) GC B cells. Thus, type I IFNs act on B cells and cDCs to drive GC formation and to coordinate IgG subclass distribution through divergent Th1 and Tfh cell-dependent pathways. |
format | Online Article Text |
id | pubmed-9326081 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93260812022-07-28 Type I Interferons Promote Germinal Centers Through B Cell Intrinsic Signaling and Dendritic Cell Dependent Th1 and Tfh Cell Lineages Dahlgren, Madelene W. Plumb, Adam W. Niss, Kristoffer Lahl, Katharina Brunak, Søren Johansson-Lindbom, Bengt Front Immunol Immunology Type I interferons (IFNs) are essential for antiviral immunity, appear to represent a key component of mRNA vaccine-adjuvanticity, and correlate with severity of systemic autoimmune disease. Relevant to all, type I IFNs can enhance germinal center (GC) B cell responses but underlying signaling pathways are incompletely understood. Here, we demonstrate that a succinct type I IFN response promotes GC formation and associated IgG subclass distribution primarily through signaling in cDCs and B cells. Type I IFN signaling in cDCs, distinct from cDC1, stimulates development of separable Tfh and Th1 cell subsets. However, Th cell-derived IFN-γ induces T-bet expression and IgG2c isotype switching in B cells prior to this bifurcation and has no evident effects once GCs and bona fide Tfh cells developed. This pathway acts in synergy with early B cell-intrinsic type I IFN signaling, which reinforces T-bet expression in B cells and leads to a selective amplification of the IgG2c(+) GC B cell response. Despite the strong Th1 polarizing effect of type I IFNs, the Tfh cell subset develops into IL-4 producing cells that control the overall magnitude of the GCs and promote generation of IgG1(+) GC B cells. Thus, type I IFNs act on B cells and cDCs to drive GC formation and to coordinate IgG subclass distribution through divergent Th1 and Tfh cell-dependent pathways. Frontiers Media S.A. 2022-07-13 /pmc/articles/PMC9326081/ /pubmed/35911733 http://dx.doi.org/10.3389/fimmu.2022.932388 Text en Copyright © 2022 Dahlgren, Plumb, Niss, Lahl, Brunak and Johansson-Lindbom https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Dahlgren, Madelene W. Plumb, Adam W. Niss, Kristoffer Lahl, Katharina Brunak, Søren Johansson-Lindbom, Bengt Type I Interferons Promote Germinal Centers Through B Cell Intrinsic Signaling and Dendritic Cell Dependent Th1 and Tfh Cell Lineages |
title | Type I Interferons Promote Germinal Centers Through B Cell Intrinsic Signaling and Dendritic Cell Dependent Th1 and Tfh Cell Lineages |
title_full | Type I Interferons Promote Germinal Centers Through B Cell Intrinsic Signaling and Dendritic Cell Dependent Th1 and Tfh Cell Lineages |
title_fullStr | Type I Interferons Promote Germinal Centers Through B Cell Intrinsic Signaling and Dendritic Cell Dependent Th1 and Tfh Cell Lineages |
title_full_unstemmed | Type I Interferons Promote Germinal Centers Through B Cell Intrinsic Signaling and Dendritic Cell Dependent Th1 and Tfh Cell Lineages |
title_short | Type I Interferons Promote Germinal Centers Through B Cell Intrinsic Signaling and Dendritic Cell Dependent Th1 and Tfh Cell Lineages |
title_sort | type i interferons promote germinal centers through b cell intrinsic signaling and dendritic cell dependent th1 and tfh cell lineages |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326081/ https://www.ncbi.nlm.nih.gov/pubmed/35911733 http://dx.doi.org/10.3389/fimmu.2022.932388 |
work_keys_str_mv | AT dahlgrenmadelenew typeiinterferonspromotegerminalcentersthroughbcellintrinsicsignalinganddendriticcelldependentth1andtfhcelllineages AT plumbadamw typeiinterferonspromotegerminalcentersthroughbcellintrinsicsignalinganddendriticcelldependentth1andtfhcelllineages AT nisskristoffer typeiinterferonspromotegerminalcentersthroughbcellintrinsicsignalinganddendriticcelldependentth1andtfhcelllineages AT lahlkatharina typeiinterferonspromotegerminalcentersthroughbcellintrinsicsignalinganddendriticcelldependentth1andtfhcelllineages AT brunaksøren typeiinterferonspromotegerminalcentersthroughbcellintrinsicsignalinganddendriticcelldependentth1andtfhcelllineages AT johanssonlindbombengt typeiinterferonspromotegerminalcentersthroughbcellintrinsicsignalinganddendriticcelldependentth1andtfhcelllineages |