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Germinal center B cells that acquire nuclear proteins are specifically suppressed by follicular regulatory T cells

Follicular regulatory T cells (Tfr) restrict development of autoantibodies and autoimmunity while supporting high-affinity foreign antigen-specific humoral response. However, whether Tfr can directly repress germinal center (GC) B cells that acquire autoantigens is unclear. Moreover, TCR specificity...

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Detalles Bibliográficos
Autores principales: Ke, Fang, Benet, Zachary L, Maz, Mitra P, Liu, Jianhua, Dent, Alexander L, Kahlenberg, Joanne Michelle, Grigorova, Irina L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9981149/
https://www.ncbi.nlm.nih.gov/pubmed/36862132
http://dx.doi.org/10.7554/eLife.83908
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author Ke, Fang
Benet, Zachary L
Maz, Mitra P
Liu, Jianhua
Dent, Alexander L
Kahlenberg, Joanne Michelle
Grigorova, Irina L
author_facet Ke, Fang
Benet, Zachary L
Maz, Mitra P
Liu, Jianhua
Dent, Alexander L
Kahlenberg, Joanne Michelle
Grigorova, Irina L
author_sort Ke, Fang
collection PubMed
description Follicular regulatory T cells (Tfr) restrict development of autoantibodies and autoimmunity while supporting high-affinity foreign antigen-specific humoral response. However, whether Tfr can directly repress germinal center (GC) B cells that acquire autoantigens is unclear. Moreover, TCR specificity of Tfr to self-antigens is not known. Our study suggests that nuclear proteins contain antigens specific to Tfr. Targeting of these proteins to antigen-specific B cells in mice triggers rapid accumulation of Tfr with immunosuppressive characteristics. Tfr then exert negative regulation of GC B cells with predominant inhibition of the nuclear protein-acquiring GC B cells, suggesting an important role of direct cognate Tfr-GC B cells interactions for the control of effector B cell response.
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spelling pubmed-99811492023-03-03 Germinal center B cells that acquire nuclear proteins are specifically suppressed by follicular regulatory T cells Ke, Fang Benet, Zachary L Maz, Mitra P Liu, Jianhua Dent, Alexander L Kahlenberg, Joanne Michelle Grigorova, Irina L eLife Microbiology and Infectious Disease Follicular regulatory T cells (Tfr) restrict development of autoantibodies and autoimmunity while supporting high-affinity foreign antigen-specific humoral response. However, whether Tfr can directly repress germinal center (GC) B cells that acquire autoantigens is unclear. Moreover, TCR specificity of Tfr to self-antigens is not known. Our study suggests that nuclear proteins contain antigens specific to Tfr. Targeting of these proteins to antigen-specific B cells in mice triggers rapid accumulation of Tfr with immunosuppressive characteristics. Tfr then exert negative regulation of GC B cells with predominant inhibition of the nuclear protein-acquiring GC B cells, suggesting an important role of direct cognate Tfr-GC B cells interactions for the control of effector B cell response. eLife Sciences Publications, Ltd 2023-03-02 /pmc/articles/PMC9981149/ /pubmed/36862132 http://dx.doi.org/10.7554/eLife.83908 Text en © 2023, Ke et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Microbiology and Infectious Disease
Ke, Fang
Benet, Zachary L
Maz, Mitra P
Liu, Jianhua
Dent, Alexander L
Kahlenberg, Joanne Michelle
Grigorova, Irina L
Germinal center B cells that acquire nuclear proteins are specifically suppressed by follicular regulatory T cells
title Germinal center B cells that acquire nuclear proteins are specifically suppressed by follicular regulatory T cells
title_full Germinal center B cells that acquire nuclear proteins are specifically suppressed by follicular regulatory T cells
title_fullStr Germinal center B cells that acquire nuclear proteins are specifically suppressed by follicular regulatory T cells
title_full_unstemmed Germinal center B cells that acquire nuclear proteins are specifically suppressed by follicular regulatory T cells
title_short Germinal center B cells that acquire nuclear proteins are specifically suppressed by follicular regulatory T cells
title_sort germinal center b cells that acquire nuclear proteins are specifically suppressed by follicular regulatory t cells
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9981149/
https://www.ncbi.nlm.nih.gov/pubmed/36862132
http://dx.doi.org/10.7554/eLife.83908
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