Trafficking receptor signatures define blood plasmablasts responding to tissue-specific immune challenge
Yekyung Seong, Nicole H. Lazarus, Lusijah Sutherland, Aida Habtezion, Tzvia Abramson, Xiao-Song He, Harry B. Greenberg, Eugene C. Butcher
Yekyung Seong, Nicole H. Lazarus, Lusijah Sutherland, Aida Habtezion, Tzvia Abramson, Xiao-Song He, Harry B. Greenberg, Eugene C. Butcher
View: Text | PDF
Research Article Immunology Vascular biology

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

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

×

Figure 4

Imprinted trafficking programs of plasmablasts in statistically enriched (disease- or inflammatory site–associated) clusters.

Options: View larger image (or click on image) Download as PowerPoint
Imprinted trafficking programs of plasmablasts in statistically enriched...
The phenotype of plasmablasts (PBs) in enriched clusters is shown for patients with (A) gastrointestinal infection (GI) symptoms, (B) ulcerative colitis (UC), (C) celiac disease (CeD), (D) upper respiratory infection (URI) symptoms, and (E) streptococcal infection (Strep). In each panel A–E, the Barnes-Hut t-distributed stochastic neighbor embedding (tSNE) map shows 2,000 PBs randomly selected from the patient class; statistically enriched clusters are colored. The heatmap shows trafficking receptor expression (mean fluorescence intensity) of PBs within each enriched cluster; an associated bar graph indicates the relative abundance of PBs in the enriched clusters. Conventional 2 × 2 flow cytometry plots of PBs from enriched phenotypes are displayed. For URI patients, a histogram insert illustrates staining for integrin β1 on α4β7– PBs, consistent with high α4β1 integrin expression (representative of n = 4). Cells (and bars in the histogram) from statistically enriched clusters are colored by P value as indicated (ANOVA, see Methods).