Pulmonary infection with influenza A virus induces site-specific germinal center and T follicular helper cell responses

Alexander W Boyden; Kevin L Legge; Thomas J Waldschmidt

doi:10.1371/journal.pone.0040733

Back

Pulmonary infection with influenza A virus induces site-specific germinal center and T follicular helper cell responses

Journal article

Open access

Peer reviewed

Pulmonary infection with influenza A virus induces site-specific germinal center and T follicular helper cell responses

Alexander W Boyden, Kevin L Legge and Thomas J Waldschmidt

PloS one, Vol.7(7), pp.e40733-e40733

2012

DOI: 10.1371/journal.pone.0040733

PMCID: PMC3394713

PMID: 22792401

Files and links (1)

url

https://doi.org/10.1371/journal.pone.0040733View

Published (Version of record) Open Access

Abstract

Protection from influenza A virus (IAV) challenge requires switched, high affinity Abs derived from long-lived memory B cells and plasma cells. These B cell subsets are generated in germinal centers (GCs), hallmark structures of T helper cell-driven B cell immunity. A full understanding of the GC reaction after respiratory IAV infection is lacking, as is the characterization of T follicular helper (T(FH)) cells that support GCs. Here, GC B cell and T(FH) cell responses were studied in mice following pulmonary challenge with IAV. Marked GC reactions were induced in draining lymph nodes (dLNs), lung, spleen and nasal-associated lymphoid tissue (NALT), although the magnitude and kinetics of the response was site-specific. Examination of switching within GCs demonstrated IgG2(+) cells to compose the largest fraction in dLNs, lung and spleen. IgA(+) GC B cells were infrequent in these sites, but composed a significant subset of the switched GC population in NALT. Further experiments demonstrated splenectomized mice to withstand a lethal recall challenge, suggesting the spleen to be unnecessary for long-term protection in spite of strong GC responses in this organ. Final studies showed that T(FH) cell numbers were highest in dLNs and spleen, and peaked in all sites prior to the height of the GC reaction. T(FH) cells purified from dLNs generated IL-21 and IFNγ upon activation, although CD4(+)CXCR5(-) T effector cells produced higher levels of all cytokines. Collectively, these findings reveal respiratory IAV infection to induce strong T helper cell-driven B cell responses in various organs, with each site displaying unique attributes.

Spleen - immunology

T-Lymphocytes, Helper-Inducer - metabolism

Germinal Center - immunology

CD4-Positive T-Lymphocytes - metabolism

Immunoglobulin Class Switching - immunology

Immunoglobulin G - classification

Lymph Nodes - immunology

CD4-Positive T-Lymphocytes - immunology

Lung - virology

Animals

B-Lymphocytes - immunology

Immunoglobulin G - immunology

Nasal Mucosa - immunology

T-Lymphocytes, Helper-Inducer - immunology

Immunoglobulin A - immunology

Antibodies, Viral - immunology

Immunologic Memory

Influenza A virus - immunology

Mice

Mice, Inbred BALB C

Cytokines - biosynthesis

Lung - immunology

Orthomyxoviridae Infections - immunology

Details

Title: Subtitle: Pulmonary infection with influenza A virus induces site-specific germinal center and T follicular helper cell responses
Creators: Alexander W Boyden - Interdisciplinary Graduate Program in Immunology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, United States of America
Kevin L Legge
Thomas J Waldschmidt
Resource Type: Journal article
Publication Details: PloS one, Vol.7(7), pp.e40733-e40733
DOI: 10.1371/journal.pone.0040733
PMID: 22792401
PMCID: PMC3394713
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: R01 AI071085 / NIAID NIH HHS R01 AA019438 / NIAAA NIH HHS R01AA019438 / NIAAA NIH HHS R01AI071085 / NIAID NIH HHS
Language: English
Date published: 2012
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984046823602771

Metrics

23 Record Views

62 Times Cited - Web of Science