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

19 Scopus citations

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

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Nair, N., Newell, E. W., Vollmers, C., Quake, S. R., Morton, J. M., Davis, M. M., He, X., & 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