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High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry

In-depth phenotyping of human intestinal antibody secreting cells (ASCs) and their precursors is important for developing improved mucosal vaccines. We used single-cell mass cytometry to simultaneously analyze 34 differentiation and trafficking markers on intestinal and circulating B cells. In addit...

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Autores principales: Nair, Nitya, Newell, Evan W., Vollmers, Christopher, Quake, Stephen R., Morton, John M., Davis, Mark M., He, Xiao-Song, Greenberg, Harry B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618273/
https://www.ncbi.nlm.nih.gov/pubmed/25899688
http://dx.doi.org/10.1038/mi.2015.36
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author Nair, Nitya
Newell, Evan W.
Vollmers, Christopher
Quake, Stephen R.
Morton, John M.
Davis, Mark M.
He, Xiao-Song
Greenberg, Harry B.
author_facet Nair, Nitya
Newell, Evan W.
Vollmers, Christopher
Quake, Stephen R.
Morton, John M.
Davis, Mark M.
He, Xiao-Song
Greenberg, Harry B.
author_sort Nair, Nitya
collection PubMed
description In-depth phenotyping of human intestinal antibody secreting cells (ASCs) and their precursors is important for developing improved mucosal vaccines. We used single-cell mass cytometry to simultaneously analyze 34 differentiation and trafficking markers on intestinal and circulating B cells. In addition, we labeled rotavirus double-layered particles with a metal isotope and characterized B cells specific to the rotavirus VP6 major structural protein. We describe the heterogeneity of the intestinal B cell compartment, dominated by ASCs with some phenotypic and transcriptional characteristics of long-lived plasma cells. Using principal component analysis, we visualized the phenotypic relationships between major B cell subsets in the intestine and blood, and revealed that IgM(+) memory B cells (MBCs) and naïve B cells were phenotypically related as were CD27(−) MBCs and switched MBCs. ASCs in the intestine and blood were highly clonally related, but associated with distinct trajectories of phenotypic development. VP6-specific B cells were present among diverse B cell subsets in immune donors, including naïve B cells, with phenotypes representative of the overall B cell pool. These data provide a high dimensional view of intestinal B cells and the determinants regulating humoral memory to a ubiquitous, mucosal pathogen at steady-state.
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spelling pubmed-46182732016-05-18 High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry Nair, Nitya Newell, Evan W. Vollmers, Christopher Quake, Stephen R. Morton, John M. Davis, Mark M. He, Xiao-Song Greenberg, Harry B. Mucosal Immunol Article In-depth phenotyping of human intestinal antibody secreting cells (ASCs) and their precursors is important for developing improved mucosal vaccines. We used single-cell mass cytometry to simultaneously analyze 34 differentiation and trafficking markers on intestinal and circulating B cells. In addition, we labeled rotavirus double-layered particles with a metal isotope and characterized B cells specific to the rotavirus VP6 major structural protein. We describe the heterogeneity of the intestinal B cell compartment, dominated by ASCs with some phenotypic and transcriptional characteristics of long-lived plasma cells. Using principal component analysis, we visualized the phenotypic relationships between major B cell subsets in the intestine and blood, and revealed that IgM(+) memory B cells (MBCs) and naïve B cells were phenotypically related as were CD27(−) MBCs and switched MBCs. ASCs in the intestine and blood were highly clonally related, but associated with distinct trajectories of phenotypic development. VP6-specific B cells were present among diverse B cell subsets in immune donors, including naïve B cells, with phenotypes representative of the overall B cell pool. These data provide a high dimensional view of intestinal B cells and the determinants regulating humoral memory to a ubiquitous, mucosal pathogen at steady-state. 2015-04-22 2016-01 /pmc/articles/PMC4618273/ /pubmed/25899688 http://dx.doi.org/10.1038/mi.2015.36 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Nair, Nitya
Newell, Evan W.
Vollmers, Christopher
Quake, Stephen R.
Morton, John M.
Davis, Mark M.
He, Xiao-Song
Greenberg, Harry B.
High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry
title High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry
title_full High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry
title_fullStr High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry
title_full_unstemmed High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry
title_short High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry
title_sort high-dimensional immune profiling of total and rotavirus vp6-specific intestinal and circulating b cells by mass cytometry
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618273/
https://www.ncbi.nlm.nih.gov/pubmed/25899688
http://dx.doi.org/10.1038/mi.2015.36
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