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Chronic Malaria drives functional heterogenity in B cell subpopilations and expansion of unswitched atypical memory B cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE149729 | GEO | 2020/09/30

REPOSITORIES: GEO

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Chronic Malaria drives functional heterogenity in B cell subpopilations and expansion of unswitched atypical memory B cells [Malaria 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 | GSE149728 | GEO

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

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Malaria-induced interferon-? drives the expansion of Tbethi atypical memory B cells.

Project description:Many chronic infections, including malaria and HIV, are associated with a large expansion of CD21-CD27- 'atypical' memory B cells (MBCs) that exhibit reduced B cell receptor (BCR) signaling and effector functions. Little is known about the conditions or transcriptional regulators driving atypical MBC differentiation. Here we show that atypical MBCs in malaria-exposed individuals highly express the transcription factor T-bet, and that T-bet expression correlates inversely with BCR signaling and skews toward IgG3 class switching. Moreover, a longitudinal analysis of a subset of children suggested a correlation between the incidence of febrile malaria and the expansion of T-bethi B cells. The Th1-cytokine containing supernatants of malaria-stimulated PBMCs plus BCR cross linking induced T-bet expression in naïve B cells that was abrogated by neutralizing IFN-? or blocking the IFN-? receptor on B cells. Accordingly, recombinant IFN-? plus BCR cross-linking drove T-bet expression in peripheral and tonsillar B cells. Consistent with this, Th1-polarized Tfh (Tfh-1) cells more efficiently induced T-bet expression in naïve B cells. These data provide new insight into the mechanisms underlying atypical MBC differentiation.

| S-EPMC5633206 | biostudies-literature

Chronic Malaria drives functional heterogenity in B cell subpopilations and expansion of unswitched atypical memory B cells

Project description:Chronic Malaria drives functional heterogenity in B cell subpopilations and expansion of unswitched atypical memory B cells

| PRJNA629804 | ENA

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

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

| PRJNA629811 | ENA

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

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

| PRJNA629812 | ENA

The epigenetic regulator Uhrf1 facilitates functional expansion of colonic regulatory T cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Expansion of an FCRL5+ B cell subset resembling atypical memory B cells in an animal model of malaria

Project description:Background: In human malaria, parasites of the genus Plasmodium elicit expansion of atypical memory B cells (atMBCs), which lack the classical markers CD21 and CD27. We have identified a putative population of analogous B cells in a murine model of infection with P. chabaudi, delineated by the marker FCRL5. We performed RNA-Seq on FCRL5+ and FCRL5- B cells sorted from infected mice, so as to characterize the transcriptional profile of these cells and permit comparison to atMBCs in humans. Results: FCRL5+ B cells were found to have distinct transcriptional profiles from FCRL5- B cells, with approximately 400 genes exhibiting significant differences between the two groups. Additionally, about 25% of these differentially expressed genes were also differentially expressed in human atMBCs versus classical MBCs, as previously described by Sullivan et al (PLoS Pathogens 2015). Conclusions: FCRL5+ class-switched B cells are a transcriptionally distinct subset arising in P. chabaudi infection, with transcriptional similarities to human atMBCs that develop in chronic malaria settings.

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Project description:This SuperSeries is composed of the SubSeries listed below.

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CX3CR1/Fractalkine receptor expression separates memory CD8+ T cells with distinct functional profiles

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-06-10 | E-GEOD-63147 | biostudies-arrayexpress