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Review
. 2016 Jun 30:7:258.
doi: 10.3389/fimmu.2016.00258. eCollection 2016.

Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung

Ji Young Hwang  1 , Troy D Randall  1 , Aaron Silva-Sanchez  1
Affiliations
Review

Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung

Ji Young Hwang et al. Front Immunol. .

Abstract

Following pulmonary inflammation, leukocytes that infiltrate the lung often assemble into structures known as inducible Bronchus-Associated Lymphoid Tissue (iBALT). Like conventional lymphoid organs, areas of iBALT have segregated B and T cell areas, specialized stromal cells, high endothelial venules, and lymphatic vessels. After inflammation is resolved, iBALT is maintained for months, independently of inflammation. Once iBALT is formed, it participates in immune responses to pulmonary antigens, including those that are unrelated to the iBALT-initiating antigen, and often alters the clinical course of disease. However, the mechanisms that govern immune responses in iBALT and determine how iBALT impacts local and systemic immunity are poorly understood. Here, we review our current understanding of iBALT formation and discuss how iBALT participates in pulmonary immunity.

Keywords: ectopic lymphoid organ; germinal center; inducible bronchus-associated lymphoid tissue; lymphoid neogenesis; tertiary lymphoid organ.

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Figures

Figure 1
Figure 1
The structure of iBALT. C57BL/6 mice were intranasally administered LPS on days 3, 5, 7, 9, and 11 after birth, and lungs were obtained 6 weeks after the last LPS administration. (A) Frozen sections were probed with anti-CD3 (red), anti-CD11c (green), and anti-B220 (Blue), and images were acquired on a Nikon Eclipse Ti microscope using the 20× objective. The dashed line indicates the position of a blood vessel. Scale bar indicates 200 μm. (B) Frozen sections were probed with anti-CD21/35 (red), peanut agglutinin (PNA - green), and anti-B220 (blue), and images were acquired on a Nikon Eclipse Ti microscope using the 20× objective. Scale bar indicates 200 μm.
Figure 2
Figure 2
Model of iBALT development. The development of iBALT can be initiated by a wide variety of stimuli, including microbial products, bacteria, viruses, allergens, tumors, and particulates (left side), which trigger the activation and cytokine production from epithelial cells and dendritic cells. Innate cells, such as ILCs and γδT cells, become activated and produce cytokines and chemokines that attract inflammatory cells like neutrophils, monocytes, and eosinophils. Granulocytes produce cytokines that promote B cell activation as well as proteases and reactive oxygen that activate stromal cell precursors. These activities would all occur during an inflammatory process. Once mature B and T cells are recruited to the lung, they reinforce the differentiation of stromal cells into mature FDCs and FRCs that respectively support the B and T cell areas of iBALT. Once inflammation is resolved, the lymphocytes, dendritic cells, and stromal cells can maintain the iBALT structure using homeostatic mechanisms – lymphotoxin and chemokines – for months.
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