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
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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

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Figure 3

Distribution of plasmablasts among tSNE-defined clusters.

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Distribution of plasmablasts among tSNE-defined clusters. (A) Heatmap il...
(A) Heatmap illustrating the number of plasmablasts (PBs) in each cluster for each individual patient (n = 52). Barnes-Hut t-distributed stochastic neighbor embedding (tSNE)-defined clusters are indicated on the x axis and ordered by unsupervised hierarchical clustering via Pearson’s correlation of cluster PB profiles (profiles of PB frequencies in the cluster for all patients). Colored branches of the dendrogram indicate clusters that are statistically enriched for a given patient class as indicated (ANOVA). (B) Pairwise Pearson’s (linear) correlation of patient PB cluster profiles (percentage of each patient’s PBs in the tSNE-defined clusters). The tSNE cluster profile of patient URI_N023, indicated by the red arrow, was an outlier compared with other URI patients, and thus excluded from subsequent analyses. GI, gastrointestinal infection; UC, ulcerative colitis; CeD, celiac disease; URI, upper respiratory infection; Strep, streptococcal infection; TIV, intramuscular trivalent influenza vaccination; ID-TIV, intradermal TIV; HD, healthy donor.