Role of iBALT in Respiratory Immunity

Abstract

Pulmonary respiration inevitably exposes the mucosal surface of the lung to potentially noxious stimuli, including pathogens, allergens, and particulates, each of which can trigger pulmonary damage and inflammation. As inflammation resolves, B and T lymphocytes often aggregate around large bronchi to form inducible Bronchus-Associated Lymphoid Tissue (iBALT). iBALT formation can be initiated by a diverse array of molecular pathways that converge on the activation and differentiation of chemokine-expressing stromal cells that serve as the scaffolding for iBALT and facilitate the recruitment, retention, and organization of leukocytes. Like conventional lymphoid organs, iBALT recruits naïve lymphocytes from the blood, exposes them to local antigens, in this case from the airways, and supports their activation and differentiation into effector cells. The activity of iBALT is demonstrably beneficial for the clearance of respiratory pathogens; however, it is less clear whether it dampens or exacerbates inflammatory responses to non-infectious agents. Here, we review the evidence regarding the role of iBALT in pulmonary immunity and propose that the final outcome depends on the context of the disease.

Redefining CD4 T cell residency: Helper T cells orchestrate protective humoral immunity in the lung

“…Taken together with our observations, these findings suggest that TRH cells maintain the plasticity to differentiate into Th1 effectors following challenge infection, an idea that is supported by our trajectory analysis and adoptive transfer experiments. The ability of TRH cells to differentiate into multipotent effectors is similar to stem-like TFH memory cells which were recently reported to generate diverse effectors following secondary infection26 .Influenza infection results in the development of iBALT, a tertiary lymphoid structure (TLS) in the lung which can act as an immunological hub, promoting rapid and localized immune responses following secondary infection49 . Compared to TRM1 cells, we 20 detected tight localization of TRH cells and B cells within iBALT cores.…”

Lung-resident memory B cells protect against bacterial pneumonia

“…Notably, influenza generates long-lasting iBALT in mice (11). Like other organized lymphoid structures, iBALT has been shown to support MBCs and plasma cells but is not a typical feature of healthy adult human lungs (12,13). Lungs of rhesus macaques recovered from asymptomatic H1N1 influenza infection are enriched for TRM but not BRM cells, a finding attributed to the likely lack of iBALT in such low-virulence infections (14).…”

“…Thus, B cells in the lungs of experienced mice were in the connective tissue of distal bronchovascular bundles, proximal to bronchiolar airways, often but not always in association with CD4 + T cells. To assess whether the high endothelial venules (HEVs) characteristic of tertiary lymphoid organs were present in experienced mouse lungs, we stained lung sections for CD34 and peripheral node addressin (PNAd), which costain HEVs in well-organized lymphoid structures such as lymph nodes (Supplemental Figure 1A; supplemental material available online with this article; https://doi.org/10.1172/JCI141810DS1) and lung iBALT (12). Although the lung sections stained brightly for the vascular endothelial marker CD34, we did not observe PNAd staining, indicating that HEVs were not present in these lung sections (Supplemental Figure 1, B-D).…”

Fantastic IgA plasma cells and where to find them

“…While IgA + PC in the lung LP can be isolated from naive animals 131 and healthy human controls, 132 their numbers are relatively low in the absence of inflammation. This changes during viral or bacterial pulmonary infections, where inducible bronchus‐associated lymphoid tissues (iBALT) form in the lungs and can become sites for harboring IgA PC 133 …”