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Inducible bronchus-associated lymphoid tissues (iBALT) serve as sites of B cell selection and maturation following influenza infection in mice

ABSTRACT: Inducible bronchus-associated lymphoid tissues (iBALT) serve as sites of B cell selection and maturation following influenza infection in mice

PROVIDER: PRJNA511864 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8369960.fastq.gz	Fastqsanger.gz
	SRR8369951.fastq.gz	Fastqsanger.gz
	SRR8369961.fastq.gz	Fastqsanger.gz
	SRR8369952.fastq.gz	Fastqsanger.gz
	SRR8369962.fastq.gz	Fastqsanger.gz

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Inducible bronchus-associated lymphoid tissues (iBALT) serve as sites of B cell selection and maturation following influenza infection in mice

Project description:GC-like structures within iBALT serve as a distinct niche that independently support the maturation and selection of B cells primarily targeted against the influenza virus nucleoprotein. Our findings suggest that iBALT, which are positioned at the frontline of the lung mucosa, drive long-lived and unique GC reactions that contribute to the diversity of the humoral response targeting influenza.

2019-03-14 | GSE124369 | GEO

Inducible Bronchus-Associated Lymphoid Tissues (iBALT) Serve as Sites of B Cell Selection and Maturation Following Influenza Infection in Mice.

Project description:Seasonally recurrent influenza virus infections are a significant cause of global morbidity and mortality. In murine models, primary influenza infection in the respiratory tract elicits potent humoral responses concentrated in the draining mediastinal lymph node and the spleen. In addition to immunity within secondary lymphoid organs (SLO), pulmonary infection is also associated with formation of ectopic inducible bronchus-associated tissues (iBALT) in the lung. These structures display a lymphoid organization, but their function and protective benefits remain unclear. Here we examined the phenotype, transcriptional profile and antigen specificity of B cell populations forming iBALT in influenza infected mice. We show that the cellular composition of iBALT was comparable to SLO, containing populations of follicular dendritic cells (FDC), T-follicular helper (Tfh) cells, and germinal center (GC)-like B cells with classical dark- and light-zone polarization. Transcriptional profiles of GC B cells in iBALT and SLO were conserved regardless of anatomical localization. The architecture of iBALT was pleiomorphic and less structurally defined than SLO. Nevertheless, we show that GC-like structures within iBALT serve as a distinct niche that independently support the maturation and selection of B cells primarily targeted against the influenza virus nucleoprotein. Our findings suggest that iBALT, which are positioned at the frontline of the lung mucosa, drive long-lived, and unique GC reactions that contribute to the diversity of the humoral response targeting influenza.

| S-EPMC6450362 | biostudies-literature

Gut-Resident IL10+CX3CR1hi Macrophages Induce Tertiary Lymphoid Structures and IgA Response in Situ

Project description:Gut resident IL10+CX3CR1hi macrophages drive development of mucosal tertiary lymphoid structures that serve as ectopic site of the IgA response to enteric infection.

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Transcriptional and phenotypic profile of lung-resident memory B cells induced by influenza infection

Project description:Long-lived, tissue-resident memory B cells (BRM) are established in the lungs of mice after pulmonary influenza infection. Influenza-specific BRM were localised within inducible bronchus-associated lymphoid tissues (iBALT) and displayed phenotypic and transcriptional signatures reminiscent of tissue-resident T cells, distinct from classical memory B cells in the blood or secondary lymphoid sites.

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Bi-phenotypic B-lymphoid/myeloid cells expressing low levels of Pax5 - potential targets of BAL development

Project description:Retroviral transduction of Pax5-deficient pro/preB cell lines with a doxycycline-inducible (TetON) form of the human Pax5 (huPax5) gene yielded cell clones which could be induced to different levels of huPax5 expression. Clones inducible to high levels developed B220+/CD19/+IgM+ B cells, while clones with low levels differentiated to B220+/CD19- /CD11b+/Gr-1- B-lymphoid/myeloid “bi-phenotypic” cells in vitro and in vivo. “Bi-phenotypic” cells could also be developed from high level-inducible cells by lower concentrations of doxycycline, inducing lower levels of huPax5 in vitro. Microarray analyses of genes expressed at these lower levels of huPax5 identified C/ebpα, C/ebpδ, Pu.1, Csf1r, Csf2r and Gata-3 as myeloid-related genes selectively expressed in the pro/preB cells which can develop under myeloid/lymphoid conditions to “bi-phenotypic” cells. Therefore, reduced expression of huPax5 during the induction of early lymphoid progenitors to B-lineage-committed cells can fix this cellular development at a stage that has previously been seen during embryonic development and in ALL-like “bi-phenotypic” acute leukemias (BAL).

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Project description:This phase I trial studies the side effects and best dose of monoclonal antibody therapy before stem cell transplant in treating patients with relapsed or refractory lymphoid malignancies. Radiolabeled monoclonal antibodies, such as yttrium-90 anti-CD45 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient’s bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving radiolabeled monoclonal antibody before a stem cell transplant may be an effective treatment for relapsed or refractory lymphoid malignancies.

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Project description:Influenza A viruses are single-stranded RNA viruses capable of evolving rapidly to adapt to environmental conditions. Examples include the establishment of a virus in a novel host or an adaptation to increasing immunity within the host population due to prior infection or vaccination against a circulating strain. Knowledge of the viral protein regions under positive selection is therefore crucial for surveillance. We have developed a method for detecting positively selected patches of sites on the surface of viral proteins, which we assume to be relevant for adaptive evolution. We measure positive selection based on dN/dS ratios of genetic changes inferred by considering the phylogenetic structure of the data and suggest a graph-cut algorithm to identify such regions. Our algorithm searches for dense and spatially distinct clusters of sites under positive selection on the protein surface. For the hemagglutinin protein of human influenza A viruses of the subtypes H3N2 and H1N1, our predicted sites significantly overlap with known antigenic and receptor-binding sites. From the structure and sequence data of the 2009 swine-origin influenza A/H1N1 hemagglutinin and PB2 protein, we identified regions that provide evidence of evolution under positive selection since introduction of the virus into the human population. The changes in PB2 overlap with sites reported to be associated with mammalian adaptation of the influenza A virus. Application of our technique to the protein structures of viruses of yet unknown adaptive behavior could identify further candidate regions that are important for host-virus interaction.

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