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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.

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Spatial transcriptomics reveals differences in bronchus-associated lymphoid tissue composition in stable and rejecting human lung allografts

Project description:Background: Lung allograft rejection is determined by pathologist grading of transbronchial biopsies (TBBx) according to criteria established by the International Society of Heart and Lung Transplantation (ISHLT). Lymphocytic bronchiolitis (LB), described as mononuclear cells in bronchiolar submucosa, exhibits significant histologic overlap with bronchus-associated lymphoid tissue (BALT) leading to diagnostic uncertainty. Additionally, the role of BALT in tolerance and rejection is debated. We sought to characterize lymphoid aggregates in ISHLT acute cellular rejection (ACR) grades A0 or A3 biopsies to better understand the spectrum of BALT and rejection lesions. Methods: TBBx were reviewed for the presence of BALT. Representative A0 and A3 biopsies were selected for spatial transcriptomics and multiplex immunofluorescence microscopy. Results: Spatial transcriptomics of allograft biopsies enabled unbiased identification of BALT and rejection lesions via neighborhood analysis. CXCL9/10+ T and PDL1/L2+ myeloid cell clusters were enriched in A0 BALT, while an NKG7+CD8+ T cell cluster was enriched in A3 BALT. Higher expression of CXCL9 and CXCL10 in the BALT correlated with A0 grade. Computational methods identified occult areas of lymphoid aggregates in rejecting lung parenchyma with similarity to rejection lesions. A3 BALT and rejection lesions showed substantial similarities. Immunofluorescence confirmed the key transcriptomics findings. Conclusions: This study suggests a relationship between the immune microenvironment in BALT and graft rejection. Additionally, lymphoid infiltration in allografts graded A3 may be more widespread than apparent on Hematoxylin and Eosin (H&E) stain.

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