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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/46997 |
| _version_ | 1811201286430785536 |
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| author | Hannah P Savage Kathrin Kläsener Fauna L Smith Zheng Luo Michael Reth Nicole Baumgarth |
| author_facet | Hannah P Savage Kathrin Kläsener Fauna L Smith Zheng Luo Michael Reth Nicole Baumgarth |
| author_sort | Hannah P Savage |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T02:19:33Z |
| format | Article |
| id | doaj.art-f40d19057a7b4f5183be06adfe9ac27a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:19:33Z |
| publishDate | 2019-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f40d19057a7b4f5183be06adfe9ac27a2022-12-22T03:52:10ZengeLife Sciences Publications LtdeLife2050-084X2019-08-01810.7554/eLife.46997TLR induces reorganization of the IgM-BCR complex regulating murine B-1 cell responses to infectionsHannah P Savage0https://orcid.org/0000-0002-1057-7239Kathrin Kläsener1https://orcid.org/0000-0002-5969-2553Fauna L Smith2Zheng Luo3Michael Reth4Nicole Baumgarth5https://orcid.org/0000-0002-2891-4483Center for Comparative Medicine, University of California, Davis, Davis, United States; Graduate Group in Immunology, University of California, Davis, Davis, United StatesBIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany; Department of Molecular Immunology, Institute of Biology III at the Faculty of Biology of the University of Freiburg, Freiburg, GermanyGraduate Group in Immunology, University of California, Davis, Davis, United States; Integrated Pathobiology Graduate Group, University of California, Davis, Davis, United StatesCenter for Comparative Medicine, University of California, Davis, Davis, United StatesBIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany; Department of Molecular Immunology, Institute of Biology III at the Faculty of Biology of the University of Freiburg, Freiburg, GermanyCenter for Comparative Medicine, University of California, Davis, Davis, United States; Graduate Group in Immunology, University of California, Davis, Davis, United States; Integrated Pathobiology Graduate Group, University of California, Davis, Davis, United States; Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, United StatesIn 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.https://elifesciences.org/articles/46997CD5B-1 CellsIgMinfluenzaSalmonella |
| spellingShingle | Hannah P Savage Kathrin Kläsener Fauna L Smith Zheng Luo Michael Reth Nicole Baumgarth TLR induces reorganization of the IgM-BCR complex regulating murine B-1 cell responses to infections eLife CD5 B-1 Cells IgM influenza Salmonella |
| 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 | CD5 B-1 Cells IgM influenza Salmonella |
| url | https://elifesciences.org/articles/46997 |
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