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B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota
B-1a cells play an important role in mediating tissue homeostasis and protecting against infections. They are the main producers of ‘natural’ IgM, spontaneously secreted serum antibodies predominately reactive to self antigens, like phosphatidylcholine (PtC), or antigens expressed by the intestinal...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703855/ https://www.ncbi.nlm.nih.gov/pubmed/31433298 http://dx.doi.org/10.7554/eLife.47015 |
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author | Kreuk, Lieselotte SM Koch, Meghan A Slayden, Leianna C Lind, Nicholas A Chu, Sophia Savage, Hannah P Kantor, Aaron B Baumgarth, Nicole Barton, Gregory M |
author_facet | Kreuk, Lieselotte SM Koch, Meghan A Slayden, Leianna C Lind, Nicholas A Chu, Sophia Savage, Hannah P Kantor, Aaron B Baumgarth, Nicole Barton, Gregory M |
author_sort | Kreuk, Lieselotte SM |
collection | PubMed |
description | B-1a cells play an important role in mediating tissue homeostasis and protecting against infections. They are the main producers of ‘natural’ IgM, spontaneously secreted serum antibodies predominately reactive to self antigens, like phosphatidylcholine (PtC), or antigens expressed by the intestinal microbiota. The mechanisms that regulate the B-1a immunoglobulin (Ig) repertoire and their antibody secretion remain poorly understood. Here, we use a novel reporter mouse to demonstrate that production of self- and microbiota-reactive antibodies is linked to BCR signaling in B-1a cells. Moreover, we show that Toll-like receptors (TLRs) are critical for shaping the Ig repertoire of B-1a cells as well as regulating their antibody production. Strikingly, we find that both the colonization of a microbiota as well as microbial-sensing TLRs are required for anti-microbiota B-1a responses, whereas nucleic-acid sensing TLRs are required for anti-PtC responses, demonstrating that linked activation of BCR and TLRs controls steady state B-1a responses to both self and microbiota-derived antigens. |
format | Online Article Text |
id | pubmed-6703855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-67038552019-08-22 B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota Kreuk, Lieselotte SM Koch, Meghan A Slayden, Leianna C Lind, Nicholas A Chu, Sophia Savage, Hannah P Kantor, Aaron B Baumgarth, Nicole Barton, Gregory M eLife Immunology and Inflammation B-1a cells play an important role in mediating tissue homeostasis and protecting against infections. They are the main producers of ‘natural’ IgM, spontaneously secreted serum antibodies predominately reactive to self antigens, like phosphatidylcholine (PtC), or antigens expressed by the intestinal microbiota. The mechanisms that regulate the B-1a immunoglobulin (Ig) repertoire and their antibody secretion remain poorly understood. Here, we use a novel reporter mouse to demonstrate that production of self- and microbiota-reactive antibodies is linked to BCR signaling in B-1a cells. Moreover, we show that Toll-like receptors (TLRs) are critical for shaping the Ig repertoire of B-1a cells as well as regulating their antibody production. Strikingly, we find that both the colonization of a microbiota as well as microbial-sensing TLRs are required for anti-microbiota B-1a responses, whereas nucleic-acid sensing TLRs are required for anti-PtC responses, demonstrating that linked activation of BCR and TLRs controls steady state B-1a responses to both self and microbiota-derived antigens. eLife Sciences Publications, Ltd 2019-08-21 /pmc/articles/PMC6703855/ /pubmed/31433298 http://dx.doi.org/10.7554/eLife.47015 Text en © 2019, Kreuk 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 Kreuk, Lieselotte SM Koch, Meghan A Slayden, Leianna C Lind, Nicholas A Chu, Sophia Savage, Hannah P Kantor, Aaron B Baumgarth, Nicole Barton, Gregory M B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota |
title | B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota |
title_full | B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota |
title_fullStr | B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota |
title_full_unstemmed | B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota |
title_short | B cell receptor and Toll-like receptor signaling coordinate to control distinct B-1 responses to both self and the microbiota |
title_sort | b cell receptor and toll-like receptor signaling coordinate to control distinct b-1 responses to both self and the microbiota |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703855/ https://www.ncbi.nlm.nih.gov/pubmed/31433298 http://dx.doi.org/10.7554/eLife.47015 |
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