Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity

Matsumoto, Rei; Gray, Joshua P.; Rybkina, Ksenia; Oppenheimer, H. R.; Levy, Louis; Friedman, Lilach M.; Khamaisi, Mogher; Meng, Wenzhao; Rosenfeld, Aaron M.; Guyer, Rebecca; Bradley, Marissa C.; Chen, David; Atkinson, Mark A.; Brusko, Todd M.; Connors, Thomas J.; Prak, Eline Luning; Hershberg, Uri; Sims, Peter A.; Hertz, Tomer; Farber, Donna L.

doi:10.1038/s41590-023-01557-3

Cited by 22 publications

(14 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To confirm that the changes in lung-resident B cell responses seen in the cKO mice were due to immune reactions occurring in the lungs, we performed immunofluorescence analysis of B cells in the lung tissue, isolated from mice at day 16 post infection ( Figure 4A ). The generation of inducible bronchus-associated lymphoid tissues (iBALT) in the lungs after influenza infection, has been previously described and these structures are known to be associated with GC cells 27,28 . Therefore, we hypothesized that the increased B cell responses in the cKO mice could be associated with iBALT structures in the lungs and we investigated whether the cKO mice have, either an increased number or better defined iBALT associated GC structures in the lungs, compared to the lungs from control mice.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have shown that upon influenza infection, structures with similar compartmentalization and cellular composition to secondary lymphoid organs, termed iBALT, are ectopically generated in the lungs of mice and support GC B cell proliferation 28,35 . Although the presence of iBALT in healthy adult humans has been controversial and may be associated with increased pathogenesis in respiratory tract diseases 36 , a recent study has shown that these iBALT associated GC structures are present in lungs from children and are involved in respiratory virus immune response 27 . Thus, multiple studies suggest that antigen-derived iBALT development support B cell proliferation and maturation in the context of respiratory pathogens 37,38 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

B cell αv integrin regulates germinal center derived lung-resident IgA B cell responses following influenza virus infection

Montiel-Armendariz,

Roe,

Lagos-Orellana

et al. 2024

Preprint

View full text Add to dashboard Cite

Emerging studies have highlighted the importance of tissue-resident B cells in the lungs for protective immunity against respiratory viruses. However, mechanisms controlling maintenance of B cell responses at respiratory sites such as lungs remain obscure. We have previously shown that the αv family of integrins limit B cell responses to antigens containing Toll-like receptor ligands, therefore deletion of B cell αv integrins in mice, enhances long-lived B cell responses against viral antigens, after systemic immunization. Here, we investigated whether αv can also regulate B cell responses at the respiratory tract, during viral infection. Our data show that αv integrin restricts development of lung-resident B cells and loss of B cell αv promotes generation of lung-resident IgA B cell responses following influenza A virus (IAV) infection of mice. Analysis of infection induced B cells in the lungs showed that loss of B cell αv promotes persistence of germinal center (GC) reactions locally in the lungs, leading to increases in lung-resident IgA+ GC and memory B cells, cross-reactive to antigenic variants. Thus, these studies reveal how IgA B cells are maintained in the lungs and point to a new strategy to improve the durability of lung-resident B cell responses for IAV vaccine efficacy.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

B cell αv integrin regulates germinal center derived lung-resident IgA B cell responses following influenza virus infection

Montiel-Armendariz,

Roe,

Lagos-Orellana

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Prior work using scRNA-seq data and the CellTypist common reference dataset discovered previously underappreciated organ-specific features and aggregates of T cells and B cells 75 . Recent publications in the field of mucosal immunology illustrate the segregation of immune cells within aggregates in human lung tissue and their role in abnormal regulation of vascular function 76,77,78,79 . Molecular and cellular changes, including fibrotic and immune-cell rich regions were recently imaged in the lungs of children with bronchopulmonary dysplasia (BPD), a chronic lung disease following premature birth 80 .…”

Section: Perivascular Immune Cells In Lungmentioning

confidence: 99%

Human BioMolecular Atlas Program (HuBMAP): 3D Human Reference Atlas Construction and Usage

Börner,

Blood,

Silverstein

et al. 2024

Preprint

View full text Add to dashboard Cite

The Human BioMolecular Atlas Program (HuBMAP) aims to construct a reference 3D structural, cellular, and molecular atlas of the healthy adult human body. The HuBMAP Data Portal (https://portal.hubmapconsortium.org) serves experimental datasets and supports data processing, search, filtering, and visualization. The Human Reference Atlas (HRA) Portal (https://humanatlas.io) provides open access to atlas data, code, procedures, and instructional materials. Experts from more than 20 consortia are collaborating to construct the HRA's Common Coordinate Framework (CCF), knowledge graphs, and tools that describe the multiscale structure of the human body (from organs and tissues down to cells, genes, and biomarkers) and to use the HRA to understand changes that occur at each of these levels with aging, disease, and other perturbations. The 6th release of the HRA v2.0 covers 36 organs with 4,499 unique anatomical structures, 1,195 cell types, and 2,089 biomarkers (e.g., genes, proteins, lipids) linked to ontologies. In addition, three workflows were developed to map new experimental data into the HRA's CCF. This paper describes the HRA user stories, terminology, data formats, ontology validation, unified analysis workflows, user interfaces, instructional materials, application programming interface (APIs), flexible hybrid cloud infrastructure, and demonstrates first atlas usage applications and previews.

show abstract

“…Tph cells appear to be generated even in healthy young individuals. Bronchus-associated lymphoid tissue (BALT) exists around the lung airway of infants and young child under 3 years old, but its number decreases after that ( 65 ). PD-1 hi CXCR5 − CD4 + cells exist here and are considered to be involved in B cell help in the lung to establish infant-acquired immunity ( 65 ).…”

Section: Diversity Of Tph Cellsmentioning

confidence: 99%

“…Bronchus-associated lymphoid tissue (BALT) exists around the lung airway of infants and young child under 3 years old, but its number decreases after that ( 65 ). PD-1 hi CXCR5 − CD4 + cells exist here and are considered to be involved in B cell help in the lung to establish infant-acquired immunity ( 65 ). These findings suggest CD4 + T cells with a Tph feature develop even under physiological conditions.…”

Section: Diversity Of Tph Cellsmentioning

confidence: 99%

Peripheral helper T cells, mavericks of peripheral immune responses

Yoshitomi

2023

International Immunology

View full text Add to dashboard Cite

Peripheral helper T (Tph) cells have been established, through intensive efforts to elucidate local immune responses in human rheumatoid arthritis (RA), as a CD4 subset intimately involved in acquired immunity in peripheral tissues. Initially, Tph cells were noted as a CD4 population that produces high levels of CXCL13 in RA synovial tissues, followed by a demonstration of their ability to help B cells. In contrast to follicular helper T (Tfh) cells, Tph cells do not express the transcription factor BCL6 but express molecules such as CXCL13, IL-21, and ICOS to help B cells in peripheral tissues. Subsequent studies showed that Tph cells are associated with various diseases, including autoimmune diseases, infections, and malignancies and with the development of early life immunity. This review summarizes the phenotype and function of Tph cells in RA and discusses their differentiation and diversity in various conditions.

show abstract

Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity

Cited by 22 publications

References 66 publications

B cell αv integrin regulates germinal center derived lung-resident IgA B cell responses following influenza virus infection

B cell αv integrin regulates germinal center derived lung-resident IgA B cell responses following influenza virus infection

Human BioMolecular Atlas Program (HuBMAP): 3D Human Reference Atlas Construction and Usage

Peripheral helper T cells, mavericks of peripheral immune responses

Contact Info

Product

Resources

About