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Trafficking receptor signatures define blood plasmablasts responding to tissue-specific immune challenge
Yekyung Seong, … , Harry B. Greenberg, Eugene C. Butcher
Yekyung Seong, … , Harry B. Greenberg, Eugene C. Butcher
Published March 23, 2017
Citation Information: JCI Insight. 2017;2(6):e90233. https://doi.org/10.1172/jci.insight.90233.
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Research Article Immunology Vascular biology

Trafficking receptor signatures define blood plasmablasts responding to tissue-specific immune challenge

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Abstract

Antibody-secreting cells are generated in regional lymphoid tissues and traffic as plasmablasts (PBs) via lymph and blood to target sites for local immunity. We used multiparameter flow cytometry to define PB trafficking programs (TPs, combinations of adhesion molecules and chemoattractant receptors) and their imprinting in patients in response to localized infection or immune insults. TPs enriched after infection or autoimmune inflammation of mucosae correlate with sites of immune response or symptoms, with different TPs imprinted during small intestinal, colon, throat, and upper respiratory immune challenge. PBs induced after intramuscular or intradermal influenza vaccination, including flu-specific antibody–secreting cells, display TPs characterized by the lack of mucosal homing receptors. PBs of healthy donors display diverse mucosa-associated TPs, consistent with homeostatic immune activity. Identification of TP signatures of PBs may facilitate noninvasive monitoring of organ-specific immune responses.

Authors

Yekyung Seong, Nicole H. Lazarus, Lusijah Sutherland, Aida Habtezion, Tzvia Abramson, Xiao-Song He, Harry B. Greenberg, Eugene C. Butcher

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Figure 5

Intramuscular and intradermal influenza vaccinations induce influenza-antigen–specific IgG plasmablasts that lack mucosal trafficking programs.

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Intramuscular and intradermal influenza vaccinations induce influenza-an...
The phenotype of plasmablasts (PBs) in enriched clusters is shown for patients receiving (A) intramuscular trivalent influenza vaccination (TIV, n = 7) or (B) intradermal TIV (ID-TIV, n = 5). tSNE, Barnes-Hut t-distributed stochastic neighbor embedding. See the Figure 4 legend for explanation of figure panels and statistics. (C) α4β7 expression by flu-Ag–specific antibody-secreting cells (ASCs). Shown is the percentage of the total recovered flu-Ag–specific ASCs among sorted α4β7-positive or -negative fractions of IgA-secreting cells (IgA ASCs) or IgG-secreting cells (IgG ASCs). Each data point is from an individual patient (n = 4). (D) The fraction of flu-Ag–specific IgG ASCs among α4β7–IgA– PBs that sorted with CCR10+ or CCR10– subsets (n = 5). In C and D, P values were determined by paired-ratio, 1-tailed t test.

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