Dataset Information

B cell profiling in malaria reveals expansion and remodelling of CD11c+ B cell subsets.

ABSTRACT: Humoral immunity is important in limiting clinical disease in malaria, yet the longitudinal B cell response to infection remains unclear. We performed a 1-year prospective study in patients treated for acute P. falciparum malaria for the first time, or with previous exposure to the disease. Using an unbiased exploratory approach with mass cytometry, followed by targeted flow cytometry, we found that ~80% of mature B cells that proliferated in response to acute infection expressed CD11c. Only ~40% of CD11c+ B cells displayed an atypical B cell phenotype, with the remaining cells primarily made up of activated- and resting memory B cells. The CD11c+ B cells expanded rapidly following infection, with previous exposure to malaria resulting in a significantly larger increase compared to individuals with primary infection. This was attributed to an expansion of switched CD11c+ B cells that was absent in primary infected individuals. The rate of contraction of the CD11c+ B cell compartment was independent of previous exposure to malaria and displayed a slow decay with a half-life of ~300 days. Collectively, these results identify CD11c as a marker of B cells responding to malaria and further highlight differences in primary- and secondary B cell responses during infection.

SUBMITTER: Sundling C

PROVIDER: S-EPMC6538354 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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B cell profiling in malaria reveals expansion and remodelling of CD11c+ B cell subsets.

Sundling Christopher C Rönnberg Caroline C Yman Victor V Asghar Muhammad M Jahnmatz Peter P Lakshmikanth Tadepally T Chen Yang Y Mikes Jaromir J Forsell Mattias N MN Sondén Klara K Achour Adnane A Brodin Petter P Persson Kristina Em KE Färnert Anna A

JCI insight 20190402

Humoral immunity is important in limiting clinical disease in malaria, yet the longitudinal B cell response to infection remains unclear. We performed a 1-year prospective study in patients treated for acute P. falciparum malaria for the first time, or with previous exposure to the disease. Using an unbiased exploratory approach with mass cytometry, followed by targeted flow cytometry, we found that ~80% of mature B cells that proliferated in response to acute infection expressed CD11c. Only ~40 ...[more]

PMID: 30939125

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Project description:BackgroundCladribine is a highly effective immunotherapy that is applied in two short-term courses over 2 years and reduces relapse rate and disease progression in patients with relapsing multiple sclerosis (MS). Despite the short treatment period, cladribine has a long-lasting effect on disease activity even after recovery of lymphocyte counts, suggesting a yet undefined long-term immune modulating effect.ObjectivesOur aim was to provide a more profound understanding of the detailed effects of cladribine, also with regard to the patients' therapy response.DesignWe performed an open-labeled, explorative, prospective, single-arm study, in which we examined the detailed lymphocyte subset development of MS patients who received cladribine treatment over 2 years.MethodsWe performed in-depth profiling of the effects of cladribine on peripheral blood lymphocytes by flow cytometry, bulk RNA sequencing of sorted CD4+ T cells, CD8+ T cells, and CD19+ B cells as well as single-cell RNA sequencing of peripheral blood mononuclear cells in a total of 23 MS patients before and at different time points up to 24 months after cladribine treatment. Data were correlated with clinical and cranial magnetic resonance imaging (MRI) disease activity.ResultsFlow cytometry revealed a predominant and sustained reduction of memory B cells compared to other B cell subsets after cladribine treatment, whereas T cell subsets were slightly reduced in a more uniform pattern. The overall transcriptional profile of total blood B cells exhibited reduced expression of proinflammatory and T cell activating genes, while single-cell transcriptomics revealed that gene expression within each B cell cluster did not change over time. Stable patients displayed stronger reductions of selected memory B cell clusters as compared to patients with clinical or cerebral MRI disease activity.ConclusionWe describe a pronounced and sustained effect of cladribine on the memory B cell compartment, and the resulting change in B cell subset composition causes a significant alteration of B cell transcriptional profiles resulting in reduced proinflammatory and T cell activating capacities. The extent of reduction in selected memory B cell clusters by cladribine may predict treatment response.

Dataset Information

B cell profiling in malaria reveals expansion and remodelling of CD11c+ B cell subsets.

Publications

B cell profiling in malaria reveals expansion and remodelling of CD11c+ B cell subsets.

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