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 6

Representation of tissue-specific trafficking programs on plasmablasts (PBs) and memory B cells in patients.

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Representation of tissue-specific trafficking programs on plasmablasts (...
Each graph presents the percentage of patients’ cells imprinted with the indicated tissue-selective trafficking programs (TPs). Graphs of percentage of indicated cell types that display (A) ulcerative colitis (UC), (B) celiac disease (CeD), (C) upper respiratory infection (URI), (D) streptococcal infection (Strep), and (E) trivalent influenza vaccination (TIV)–associated and intradermal TIV (ID-TIV)–associated TPs. Patient samples, including healthy donors (HDs) and patients with gastrointestinal infection (GI), are grouped according to their disease class (indicated on the x axis). IgA+ PBs (indicated by open “A” on the abscissa), IgA– PBs (G) or IgA+ memory B cells (M) are evaluated separately. Each data point is from an individual patient (n = 52), and represents the percentage of the indicated cell type that displays a pattern of trafficking receptors characteristic of PBs in statistically enriched TP clusters (P < 0.005, from Figure 4) in the disease class evaluated in the graph. *P < 0.05, **P < 0.005, ***P < 0.0005 by 2-way ANOVA.