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Compartmentalization of human B cell responses in early life through induction of bronchus-associated lymphoid tissue

ABSTRACT: Compartmentalization of human B cell responses in early life through induction of bronchus-associated lymphoid tissue

PROVIDER: PRJNA927026 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23214107_1.fastq.gz	Fastqsanger.gz
	SRR23214107_2.fastq.gz	Fastqsanger.gz
	SRR23214108_1.fastq.gz	Fastqsanger.gz
	SRR23214108_2.fastq.gz	Fastqsanger.gz
	SRR23214109_1.fastq.gz	Fastqsanger.gz

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Compartmentalization of human B cell responses in early life through induction of bronchus-associated lymphoid tissue

Project description:Infants and young children are more susceptible to common respiratory pathogens compared to adults, but can fare better against novel pathogens like SARS-CoV-2. The mechanisms by which infants and young children mount effective responses to respiratory pathogens are unknown. Here, we demonstrate through study of lungs and lung-associated lymph nodes (LLN) from infant and pediatric organ donors, aged 0-13 years, that bronchus-associated lymphoid tissue (BALT), develops in lungs during the first year of life. BALT structures, consisting of B cell follicles and T cell zones, increase in numbers in the early years, and subsequently decrease over childhood coincident with accumulation of memory T cells in the lung. Early life BALT contains germinal centers and supports B cell differentiation, clonal expansion, somatic hypermutation, and immunoglobulin class switching. High dimensional flow cytometry reveals seeding of lungs by newly formed B cells (transitional cells) during infancy coincident with the timing of maximal BALT formation. We further demonstrate increased lung-localized B cell responses during respiratory virus infection in infants. Together, our findings provide novel evidence for BALT as an early life adaptation for mobilizing in situ immune protection to the diverse respiratory challenges during this formative life stage.

2023-05-25 | GSE223646 | GEO

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

Project description:Infants and young children are more susceptible to common respiratory pathogens than adults but can fare better against novel pathogens like severe acute respiratory syndrome coronavirus 2. The mechanisms by which infants and young children mount effective immune responses to respiratory pathogens are unknown. Through investigation of lungs and lung-associated lymph nodes from infant and pediatric organ donors aged 0-13 years, we show that bronchus-associated lymphoid tissue (BALT), containing B cell follicles, CD4+ T cells and functionally active germinal centers, develop during infancy. BALT structures are prevalent around lung airways during the first 3 years of life, and their numbers decline through childhood coincident with the accumulation of memory T cells. Single-cell profiling and repertoire analysis reveals that early life lung B cells undergo differentiation, somatic hypermutation and immunoglobulin class switching and exhibit a more activated profile than lymph node B cells. Moreover, B cells in the lung and lung-associated lymph nodes generate biased antibody responses to multiple respiratory pathogens compared to circulating antibodies, which are mostly specific for vaccine antigens in the early years of life. Together, our findings provide evidence for BALT as an early life adaptation for mobilizing localized immune protection to the diverse respiratory challenges during this formative life stage.

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Lymphoid subsets in the AML bone marrow microenvironment following chemotherapy induction

Project description:Using scRNA-seq, bone marrow (BM) aspirates, collected post-induction, from 12 complete responders (CR) and 10 refractory patients were compared for lymphoid cells subpopulations.

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IL-22 is required for the induction of bronchus-associated lymphoid tissue in tolerant lung allografts.

Project description:Long-term survival after lung transplantation remains profoundly limited by graft rejection. Recent work has shown that bronchus-associated lymphoid tissue (BALT), characterized by the development of peripheral nodal addressin (PNAd)-expressing high endothelial venules and enriched in B and Foxp3+ T cells, is important for the maintenance of allograft tolerance. Mechanisms underlying BALT induction in tolerant pulmonary allografts, however, remain poorly understood. Here, we show that the development of PNAd-expressing high endothelial venules within intragraft lymphoid follicles and the recruitment of B cells, but not Foxp3+ cells depends on IL-22. We identify graft-infiltrating gamma-delta (γδ) T cells and Type 3 innate lymphoid cells (ILC3s) as important producers of IL-22. Reconstitution of IL-22 at late time points through retransplantation into wildtype hosts mediates B cell recruitment into lymphoid follicles within the allograft, resulting in a significant increase in their size, but does not induce PNAd expression. Our work has identified cellular and molecular requirements for the induction of BALT in pulmonary allografts during tolerance induction and may provide a platform for the development of new therapies for lung transplant patients.

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Epigenome analysis of brochoscopic paired biopsy specimens from tumoral sites and the contralateral bronchus.

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