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B cell profiling in malaria reveals expansion and remodeling of CD11c+ B cell subsets
Christopher Sundling, … , Kristina E.M. Persson, Anna Färnert
Christopher Sundling, … , Kristina E.M. Persson, Anna Färnert
Published April 2, 2019
Citation Information: JCI Insight. 2019;4(9):e126492. https://doi.org/10.1172/jci.insight.126492.
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Research Article Immunology Infectious disease

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

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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 Plasmodium 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 approximately 80% of mature B cells that proliferated in response to acute infection expressed CD11c. Only approximately 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 with 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 approximately 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.

Authors

Christopher Sundling, Caroline Rönnberg, Victor Yman, Muhammad Asghar, Peter Jahnmatz, Tadepally Lakshmikanth, Yang Chen, Jaromir Mikes, Mattias N. Forsell, Klara Sondén, Adnane Achour, Petter Brodin, Kristina E.M. Persson, Anna Färnert

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Figure 3

B cell phenotypic analysis by mass cytometry.

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B cell phenotypic analysis by mass cytometry.
(A) tSNE analysis followed...
(A) tSNE analysis followed by clustering of mass cytometry data for individual primary infected (n = 2) and previously exposed (n = 2) donors. (B) Merged tSNE plot for all donors and time points (n = 24 samples), with each cluster indicated by number and color. (C) Merged tSNE plots for each group (previously exposed: n = 11 samples; primary infection: n = 10 samples; healthy controls: n = 3 samples). (D) Heatmap showing marker expression within each cluster. Circles are colored as cluster plots. (E) Expression of CD21, CD27, and CD11c for analyzed cells. (F) Contribution of each B cell subset to total CD19+ B cells at different time points after infection. Blue solid lines indicate individuals with a primary infection; red dashed lines indicate individuals previously exposed to malaria. The dotted black line indicates the mean frequency of each population in healthy controls.

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