Inducible bronchus-associated lymphoid tissues (iBALT) serve as sites of B cell selection and maturation following influenza infection in mice

Tan, Hyon-Xhi, Esterbauer, Robyn, Vanderven, Hillary A., Juno, Jennifer A., Kent, Stephen J., and Wheatley, Adam K. (2019) Inducible bronchus-associated lymphoid tissues (iBALT) serve as sites of B cell selection and maturation following influenza infection in mice. Frontiers in Immunology, 10. 611.

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Abstract

Seasonally recurrent influenza virus infections are a significant cause of global morbidity and mortality. In murine models, primary influenza infection in the respiratory tract elicits potent humoral responses concentrated in the draining mediastinal lymph node and the spleen. In addition to immunity within secondary lymphoid organs (SLO), pulmonary infection is also associated with formation of ectopic inducible bronchus-associated tissues (iBALT) in the lung. These structures display a lymphoid organization, but their function and protective benefits remain unclear. Here we examined the phenotype, transcriptional profile and antigen specificity of B cell populations forming iBALT in influenza infected mice. We show that the cellular composition of iBALT was comparable to SLO, containing populations of follicular dendritic cells (FDC), T-follicular helper (Tfh) cells, and germinal center (GC)-like B cells with classical dark- and light-zone polarization. Transcriptional profiles of GC B cells in iBALT and SLO were conserved regardless of anatomical localization. The architecture of iBALT was pleiomorphic and less structurally defined than SLO. Nevertheless, we show that GC-like structures within iBALT serve as a distinct niche that independently support the maturation and selection of B cells primarily targeted against the influenza virus nucleoprotein. Our findings suggest that iBALT, which are positioned at the frontline of the lung mucosa, drive long-lived, and unique GC reactions that contribute to the diversity of the humoral response targeting influenza.

Item ID: 57914
Item Type: Article (Research - C1)
ISSN: 1664-3224
Keywords: germinal center (GC), influenza, iBALT, B cell, humoral immunity
Additional Information:

Copyright © 2019 Tan, Esterbauer, Vanderven, Juno, Kent and Wheatley. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Funders: National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: NHMRC program grant ID1052979, NHMRC project grant ID1129099
Date Deposited: 10 Apr 2019 07:43
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
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