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

N. Nair, E. W. Newell, C. Vollmers, S. R. Quake, J. M. Morton, M. M. Davis, Xiaosong He, H. B. Greenberg

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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 (RV) double-layered particles with a metal isotope and characterized B cells specific to the RV 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 naive 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 naive 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.

Original languageEnglish (US)
Pages (from-to)68-82
Number of pages15
JournalMucosal Immunology
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Rotavirus
B-Lymphocytes
Antibody-Producing Cells
B-Lymphocyte Subsets
Intestines
Differentiation Antigens
Plasma Cells
Principal Component Analysis
Isotopes
Immunoglobulin M
Vaccines
Metals
Phenotype

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Nair, N., Newell, E. W., Vollmers, C., Quake, S. R., Morton, J. M., Davis, M. M., ... Greenberg, H. B. (2016). High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry. Mucosal Immunology, 9(1), 68-82. https://doi.org/10.1038/mi.2015.36

High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry. / Nair, N.; Newell, E. W.; Vollmers, C.; Quake, S. R.; Morton, J. M.; Davis, M. M.; He, Xiaosong; Greenberg, H. B.

In: Mucosal Immunology, Vol. 9, No. 1, 01.01.2016, p. 68-82.

Research output: Contribution to journalArticle

Nair, N, Newell, EW, Vollmers, C, Quake, SR, Morton, JM, Davis, MM, He, X & Greenberg, HB 2016, 'High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry', Mucosal Immunology, vol. 9, no. 1, pp. 68-82. https://doi.org/10.1038/mi.2015.36
Nair, N. ; Newell, E. W. ; Vollmers, C. ; Quake, S. R. ; Morton, J. M. ; Davis, M. M. ; He, Xiaosong ; Greenberg, H. B. / High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry. In: Mucosal Immunology. 2016 ; Vol. 9, No. 1. pp. 68-82.
@article{ca5f929db2c849819f03a41bd86da317,
title = "High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry",
abstract = "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 (RV) double-layered particles with a metal isotope and characterized B cells specific to the RV 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 naive 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 naive 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.",
author = "N. Nair and Newell, {E. W.} and C. Vollmers and Quake, {S. R.} and Morton, {J. M.} and Davis, {M. M.} and Xiaosong He and Greenberg, {H. B.}",
year = "2016",
month = "1",
day = "1",
doi = "10.1038/mi.2015.36",
language = "English (US)",
volume = "9",
pages = "68--82",
journal = "Mucosal Immunology",
issn = "1933-0219",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - High-dimensional immune profiling of total and rotavirus VP6-specific intestinal and circulating B cells by mass cytometry

AU - Nair, N.

AU - Newell, E. W.

AU - Vollmers, C.

AU - Quake, S. R.

AU - Morton, J. M.

AU - Davis, M. M.

AU - He, Xiaosong

AU - Greenberg, H. B.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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 (RV) double-layered particles with a metal isotope and characterized B cells specific to the RV 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 naive 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 naive 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.

AB - 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 (RV) double-layered particles with a metal isotope and characterized B cells specific to the RV 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 naive 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 naive 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.

UR - http://www.scopus.com/inward/record.url?scp=84953220473&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84953220473&partnerID=8YFLogxK

U2 - 10.1038/mi.2015.36

DO - 10.1038/mi.2015.36

M3 - Article

C2 - 25899688

AN - SCOPUS:84953220473

VL - 9

SP - 68

EP - 82

JO - Mucosal Immunology

JF - Mucosal Immunology

SN - 1933-0219

IS - 1

ER -