Defining trafficking programs of human plasmablasts responding to tissue-specific immune challenge

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Abstract/Contents

Abstract
Antibody secreting cells are generated in regional lymphoid tissues and traffic as plasmablasts (PB) via lymph and blood to target sites for local immunity. The PB, a transiently activated population of B cells, are present in low numbers in the peripheral blood of healthy individuals. After acute infection or in setting of active immune responses, however, the frequency of blood PB increases dramatically, peaking 7 to 9 days after immunization or the onset of symptom. PB localized to target tissues undergo further maturation into antibody-secreting plasma cells. For this tissue-specific migration, the homing signature is imprinted on activated lymphocytes during their development by local environmental signals, but the trafficking mechanisms of PB remain poorly characterized. Here, we used multi-parameter flow cytometry to define trafficking programs (TPs, combinations of adhesion molecules and chemoattractant receptors) of PB, and their imprinting in patients in response to localized infection or immune insults. Using single cell-based analysis, we show that 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. PB induced after intramuscular or intradermal influenza vaccination, including flu-specific antibody secreting cells, display TPs characterized by the lack of mucosal homing receptors. PB isolated from healthy donors display diverse mucosa-associated TPs, consistent with homeostatic immune activity. Identification of TP signatures of PB may facilitate non-invasive monitoring of organ-specific immune responses.

Description

Type of resource text
Form electronic; electronic resource; remote
Extent 1 online resource.
Publication date 2016
Issuance monographic
Language English

Creators/Contributors

Associated with Seong, Yekyung
Associated with Stanford University, Program in Immunology.
Primary advisor Butcher, Eugene
Thesis advisor Butcher, Eugene
Thesis advisor Habtezion, Aida
Thesis advisor Robinson, William (William Hewitt)
Thesis advisor Wu, Joy
Advisor Habtezion, Aida
Advisor Robinson, William (William Hewitt)
Advisor Wu, Joy

Subjects

Genre Theses

Bibliographic information

Statement of responsibility Yekyung Seong.
Note Submitted to the Program in Immunology.
Thesis Thesis (Ph.D.)--Stanford University, 2016.
Location electronic resource

Access conditions

Copyright
© 2016 by Yekyung Seong
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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