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Early derivation of IgM memory cells and bone marrow plasmablasts

IgM memory cells are recognized as an important component of B cell memory in mice and humans. Our studies of B cells elicited in response to ehrlichial infection identified a population of CD11c-positive IgM memory cells, and an IgM bone marrow antibody-secreting cell population. The origin of thes...

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Autores principales: Papillion, Amber M., Kenderes, Kevin J., Yates, Jennifer L., Winslow, Gary M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456393/
https://www.ncbi.nlm.nih.gov/pubmed/28575114
http://dx.doi.org/10.1371/journal.pone.0178853
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author Papillion, Amber M.
Kenderes, Kevin J.
Yates, Jennifer L.
Winslow, Gary M.
author_facet Papillion, Amber M.
Kenderes, Kevin J.
Yates, Jennifer L.
Winslow, Gary M.
author_sort Papillion, Amber M.
collection PubMed
description IgM memory cells are recognized as an important component of B cell memory in mice and humans. Our studies of B cells elicited in response to ehrlichial infection identified a population of CD11c-positive IgM memory cells, and an IgM bone marrow antibody-secreting cell population. The origin of these cells was unknown, although an early T-independent spleen CD11c- and T-bet-positive IgM plasmablast population precedes both, suggesting a linear relationship. A majority of the IgM memory cells detected after day 30 post-infection, also T-bet-positive, had undergone somatic hypermutation, indicating they expressed activation-induced cytidine deaminase (AID). Therefore, to identify early AID-expressing precursor B cells, we infected an AID-regulated tamoxifen-inducible Cre-recombinase-EYFP reporter strain. Tamoxifen administration led to the labeling of both IgM memory cells and bone marrow ASCs on day 30 and later post-infection. High frequencies of labeled cells were identified on day 30 post-infection, following tamoxifen administration on day 10 post-infection, although IgM memory cells were marked when tamoxifen was administered as early as day 4 post-infection. Transcription of Aicda in the early plasmablasts was not detected in the absence of CD4 T cells, but occurred independently of TLR signaling. Unlike the IgM memory cells, the bone marrow IgM ASCs were elicited independent of T cell help. Moreover, Aicda was constitutively expressed in IgM memory cells, but not in bone marrow ASCs. These studies demonstrate that two distinct long-term IgM-positive B cell populations are generated early in response to infection, but are maintained via separate mechanisms.
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spelling pubmed-54563932017-06-12 Early derivation of IgM memory cells and bone marrow plasmablasts Papillion, Amber M. Kenderes, Kevin J. Yates, Jennifer L. Winslow, Gary M. PLoS One Research Article IgM memory cells are recognized as an important component of B cell memory in mice and humans. Our studies of B cells elicited in response to ehrlichial infection identified a population of CD11c-positive IgM memory cells, and an IgM bone marrow antibody-secreting cell population. The origin of these cells was unknown, although an early T-independent spleen CD11c- and T-bet-positive IgM plasmablast population precedes both, suggesting a linear relationship. A majority of the IgM memory cells detected after day 30 post-infection, also T-bet-positive, had undergone somatic hypermutation, indicating they expressed activation-induced cytidine deaminase (AID). Therefore, to identify early AID-expressing precursor B cells, we infected an AID-regulated tamoxifen-inducible Cre-recombinase-EYFP reporter strain. Tamoxifen administration led to the labeling of both IgM memory cells and bone marrow ASCs on day 30 and later post-infection. High frequencies of labeled cells were identified on day 30 post-infection, following tamoxifen administration on day 10 post-infection, although IgM memory cells were marked when tamoxifen was administered as early as day 4 post-infection. Transcription of Aicda in the early plasmablasts was not detected in the absence of CD4 T cells, but occurred independently of TLR signaling. Unlike the IgM memory cells, the bone marrow IgM ASCs were elicited independent of T cell help. Moreover, Aicda was constitutively expressed in IgM memory cells, but not in bone marrow ASCs. These studies demonstrate that two distinct long-term IgM-positive B cell populations are generated early in response to infection, but are maintained via separate mechanisms. Public Library of Science 2017-06-02 /pmc/articles/PMC5456393/ /pubmed/28575114 http://dx.doi.org/10.1371/journal.pone.0178853 Text en © 2017 Papillion et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Papillion, Amber M.
Kenderes, Kevin J.
Yates, Jennifer L.
Winslow, Gary M.
Early derivation of IgM memory cells and bone marrow plasmablasts
title Early derivation of IgM memory cells and bone marrow plasmablasts
title_full Early derivation of IgM memory cells and bone marrow plasmablasts
title_fullStr Early derivation of IgM memory cells and bone marrow plasmablasts
title_full_unstemmed Early derivation of IgM memory cells and bone marrow plasmablasts
title_short Early derivation of IgM memory cells and bone marrow plasmablasts
title_sort early derivation of igm memory cells and bone marrow plasmablasts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456393/
https://www.ncbi.nlm.nih.gov/pubmed/28575114
http://dx.doi.org/10.1371/journal.pone.0178853
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