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Shared transcriptional profiles at the single cell level of atypical memory B cells suggest common drivers of expansion and function in malaria, HIV and autoimmune diseases [Malaria VDJ+GEX scRNA-seq]

ABSTRACT: Shared transcriptional profiles at the single cell level of atypical memory B cells suggest common drivers of expansion and function in malaria, HIV and autoimmune diseases [Malaria VDJ+GEX scRNA-seq]

PROVIDER: PRJNA663561 | ENA |

REPOSITORIES: ENA

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Shared transcriptional profiles at the single cell level of atypical memory B cells suggest common drivers of expansion and function in malaria, HIV and autoimmune diseases [Malaria VDJ+GEX scRNA-seq]

Project description:Human chronic infectious diseases have been shown to alter the composition and phenotype of the B cell compartment, which, in part, can attribute to failure to acquire protective immunity. However, the extent of such alterations is poorly understood. Here, using a combination of bulk and single cell RNA-sequencing (scRNA-seq) of B cells in individuals living in malaria-endemic Africa, we characterized changes in naïve B cell, classical memory B cell (MBC) and atypical MBC subsets. Of particular interest were unswitched atypical MBCs that expanded in children upon the onset of febrile malaria. This subpopulation expressed IgD but only low levels of IgM (IgD+IgMlo), high levels of the atypical MBC markers, Tbet and CD11c, as well as the intrinsically autoreactive VH4-34. IgD+IgMlo atypical MBCs were distinguished functionally by their acquisition of high antigen-affinity thresholds for activation, suggesting the IgD+IgMlo atypical MBC expansion during febrile malaria may reduce responses to low affinity self-antigens during acute malaria

2020-09-30 | GSE157967 | GEO

Shared transcriptional profiles at the single cell level of atypical memory B cells suggest common drivers of expansion and function in malaria, HIV and autoimmune diseases [HIV scRNA-seq]

Project description:Human chronic infectious diseases, including malaria and HIV and autoimmune diseases, notably SLE, are accompanied by a striking expansion of a subpopulation of B cells termed atypical memory B cells (MBCs). We compared the single cell transcriptional profiles of B cells in malaria and HIV, characterizing and uncovering heterogeneity within each B cell subset. Remarkably, atypical MBC clusters in these two diseases showed significant similarities to each other as well as to atypical MBCs in autoimmune diseases, suggesting a common driver of their expansion and shared functions. Focusing on atypical MBCs in malaria we identified an IgD+IgMlo subpopulation that expanded in children upon the onset of febrile malaria, showed a distinct V gene usage characteristic of antigen-driven B cell populations and unexpectedly, had acquired high antigen-affinity thresholds for activation. We speculate that in malaria IgD+IgMlo atypical MBCs expand to limit responses to low-affinity self-antigens, a function that may be shared by atypical MBCs in other chronic infections and autoimmune diseases.

2020-09-30 | GSE157966 | GEO

A high-resolution single-cell multiomic atlas of the human fetal lung - scRNA / GEX / VDJ

Project description:A high-resolution single-cell multiomic atlas of the human fetal lung - scRNA / GEX / VDJ

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Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function

Project description:Plasmodium falciparum malaria is a deadly infectious disease for which we have no licensed vaccine. Antibodies confer protection against malaria and individuals exposed to P. falciparum acquire protective antibodies, but only after years of repeated infections. We recently showed that malaria exposure is associated with a large expansion of a population of atypical memory B cells (MBCs) that phenotypically resemble B cell populations expanded in chronic viral infections, including HIV. At present the relationship of atypical MBCs to classical MBCs and their function are not known. We provide evidence that the expressed VH gene repertoires and somatic hypermutation rates of atypical and classical MBCs are indistinguishable, indicating the two populations are closely related developmentally. Atypical MBCs can be distinguished by their expression of multiple inhibitory receptors, including Fc receptor-like-5. B cell receptor (BCR) signaling is stunted in atypical MBCs, resulting in impaired Ca2+ mobilization, proliferation and cytokine production. Atypical MBCs do not spontaneously secrete antibodies and cannot be stimulated to differentiate into antibody-secreting cells in vitro. These results suggest that in individuals chronically exposed to malaria, atypical MBCs differentiate from classical MBCs and assume a phenotype refractory to BCR-mediated activation, potentially contributing to the inefficient acquisition of immunity to malaria. Comparison of human atypical B cell versus classical B cell versus naïve B cell.

2015-05-07 | E-GEOD-65928 | biostudies-arrayexpress

Shared transcriptional profiles of atypical B cells suggest common drivers of expansion and function in malaria, HIV, and autoimmunity.

Project description:Chronic infectious diseases have a substantial impact on the human B cell compartment including a notable expansion of B cells here termed atypical B cells (ABCs). Using unbiased single-cell RNA sequencing (scRNA-seq), we uncovered and characterized heterogeneities in naïve B cell, classical memory B cells, and ABC subsets. We showed remarkably similar transcriptional profiles for ABC clusters in malaria, HIV, and autoimmune diseases and demonstrated that interferon-γ drove the expansion of ABCs in malaria. These observations suggest that ABCs represent a separate B cell lineage with a common inducer that further diversifies and acquires disease-specific characteristics and functions. In malaria, we identified ABC subsets based on isotype expression that differed in expansion in African children and in B cell receptor repertoire characteristics. Of particular interest, IgD+IgMlo and IgD-IgG+ ABCs acquired a high antigen affinity threshold for activation, suggesting that ABCs may limit autoimmune responses to low-affinity self-antigens in chronic malaria.

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Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function

2015-05-07 | GSE65928 | GEO

Chronic Malaria drives functional heterogenity in B cell subpopulations and expansion of unswitched atypical memory B cells [Malaria bulkRNA-seq]

2020-09-30 | GSE149727 | GEO

Chronic Malaria drives functional heterogenity in B cell subpopilations and expansion of unswitched atypical memory B cells [Malaria scRNA-seq]

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Shared transcriptional profiles at the single cell level of atypical memory B cells suggest common drivers of expansion and function in malaria, HIV and autoimmune diseases [HIV scRNA-seq]

Project description:Shared transcriptional profiles at the single cell level of atypical memory B cells suggest common drivers of expansion and function in malaria, HIV and autoimmune diseases [HIV scRNA-seq]

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VDJ-sequencing of fetal skin

Project description:VDJ-sequencing of fetal skin

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