Type I Interferons Promote Germinal Centers Through B Cell Intrinsic Signaling and Dendritic Cell Dependent Th1 and Tfh Cell Lineages
(2022) In Frontiers in Immunology 13.- Abstract
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... (More)
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.
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- author
- Dahlgren, Madelene W. LU ; Plumb, Adam W. ; Niss, Kristoffer ; Lahl, Katharina LU ; Brunak, Søren and Johansson-Lindbom, Bengt LU
- organization
- publishing date
- 2022-07-13
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- antibody responses, germinal center (GC) B cells, IgG subclass antibodies, Tfh cells, Th1 cells, Type I Interferons
- in
- Frontiers in Immunology
- volume
- 13
- article number
- 932388
- publisher
- Frontiers Media S. A.
- external identifiers
-
- scopus:85134799358
- pmid:35911733
- ISSN
- 1664-3224
- DOI
- 10.3389/fimmu.2022.932388
- language
- English
- LU publication?
- yes
- id
- bafa582f-b8d0-4f59-995c-18c1f0988887
- date added to LUP
- 2022-09-15 15:01:38
- date last changed
- 2024-09-16 06:20:29
@article{bafa582f-b8d0-4f59-995c-18c1f0988887, abstract = {{<p>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<sup>+</sup> 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<sup>+</sup> 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.</p>}}, author = {{Dahlgren, Madelene W. and Plumb, Adam W. and Niss, Kristoffer and Lahl, Katharina and Brunak, Søren and Johansson-Lindbom, Bengt}}, issn = {{1664-3224}}, keywords = {{antibody responses; germinal center (GC) B cells; IgG subclass antibodies; Tfh cells; Th1 cells; Type I Interferons}}, language = {{eng}}, month = {{07}}, publisher = {{Frontiers Media S. A.}}, series = {{Frontiers in Immunology}}, title = {{Type I Interferons Promote Germinal Centers Through B Cell Intrinsic Signaling and Dendritic Cell Dependent Th1 and Tfh Cell Lineages}}, url = {{http://dx.doi.org/10.3389/fimmu.2022.932388}}, doi = {{10.3389/fimmu.2022.932388}}, volume = {{13}}, year = {{2022}}, }