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TLR induces reorganization of the IgM-BCR complex regulating murine B-1 cell responses to infections

In mice, neonatally-developing, self-reactive B-1 cells generate steady levels of natural antibodies throughout life. B-1 cells can, however, also rapidly respond to infections with increased local antibody production. The mechanisms regulating these two seemingly very distinct functions are poorly...

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Autores principales: Savage, Hannah P, Kläsener, Kathrin, Smith, Fauna L, Luo, Zheng, Reth, Michael, Baumgarth, Nicole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703853/
https://www.ncbi.nlm.nih.gov/pubmed/31433296
http://dx.doi.org/10.7554/eLife.46997
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author Savage, Hannah P
Kläsener, Kathrin
Smith, Fauna L
Luo, Zheng
Reth, Michael
Baumgarth, Nicole
author_facet Savage, Hannah P
Kläsener, Kathrin
Smith, Fauna L
Luo, Zheng
Reth, Michael
Baumgarth, Nicole
author_sort Savage, Hannah P
collection PubMed
description In mice, neonatally-developing, self-reactive B-1 cells generate steady levels of natural antibodies throughout life. B-1 cells can, however, also rapidly respond to infections with increased local antibody production. The mechanisms regulating these two seemingly very distinct functions are poorly understood, but have been linked to expression of CD5, an inhibitor of BCR-signaling. Here we demonstrate that TLR-mediated activation of CD5+ B-1 cells induced the rapid reorganization of the IgM-BCR complex, leading to the eventual loss of CD5 expression, and a concomitant increase in BCR-downstream signaling, both in vitro and in vivo after infections of mice with influenza virus and Salmonella typhimurium. Both, initial CD5 expression and TLR-mediated stimulation, were required for the differentiation of B-1 cells to IgM-producing plasmablasts after infections. Thus, TLR-mediated signals support participation of B-1 cells in immune defense via BCR-complex reorganization.
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spelling pubmed-67038532019-08-22 TLR induces reorganization of the IgM-BCR complex regulating murine B-1 cell responses to infections Savage, Hannah P Kläsener, Kathrin Smith, Fauna L Luo, Zheng Reth, Michael Baumgarth, Nicole eLife Immunology and Inflammation In mice, neonatally-developing, self-reactive B-1 cells generate steady levels of natural antibodies throughout life. B-1 cells can, however, also rapidly respond to infections with increased local antibody production. The mechanisms regulating these two seemingly very distinct functions are poorly understood, but have been linked to expression of CD5, an inhibitor of BCR-signaling. Here we demonstrate that TLR-mediated activation of CD5+ B-1 cells induced the rapid reorganization of the IgM-BCR complex, leading to the eventual loss of CD5 expression, and a concomitant increase in BCR-downstream signaling, both in vitro and in vivo after infections of mice with influenza virus and Salmonella typhimurium. Both, initial CD5 expression and TLR-mediated stimulation, were required for the differentiation of B-1 cells to IgM-producing plasmablasts after infections. Thus, TLR-mediated signals support participation of B-1 cells in immune defense via BCR-complex reorganization. eLife Sciences Publications, Ltd 2019-08-21 /pmc/articles/PMC6703853/ /pubmed/31433296 http://dx.doi.org/10.7554/eLife.46997 Text en © 2019, Savage et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology and Inflammation
Savage, Hannah P
Kläsener, Kathrin
Smith, Fauna L
Luo, Zheng
Reth, Michael
Baumgarth, Nicole
TLR induces reorganization of the IgM-BCR complex regulating murine B-1 cell responses to infections
title TLR induces reorganization of the IgM-BCR complex regulating murine B-1 cell responses to infections
title_full TLR induces reorganization of the IgM-BCR complex regulating murine B-1 cell responses to infections
title_fullStr TLR induces reorganization of the IgM-BCR complex regulating murine B-1 cell responses to infections
title_full_unstemmed TLR induces reorganization of the IgM-BCR complex regulating murine B-1 cell responses to infections
title_short TLR induces reorganization of the IgM-BCR complex regulating murine B-1 cell responses to infections
title_sort tlr induces reorganization of the igm-bcr complex regulating murine b-1 cell responses to infections
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703853/
https://www.ncbi.nlm.nih.gov/pubmed/31433296
http://dx.doi.org/10.7554/eLife.46997
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