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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 4

B cell population dynamics by flow cytometry.

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B cell population dynamics by flow cytometry.
(A) Gating strategy of B c...
(A) Gating strategy of B cell subsets. Cells were pregated for size, singlets, and live cells. B cells were identified by CD19 and CD20 expression. CD19+CD20lo B cells were further gated for CD27 and CD38 for definition of (B) plasmablasts. CD19+CD20+ B cells were gated as CD10+ (C) immature B cells or (D and E) CD10− mature B cells. CD19+CD20+CD10− mature B cells were further separated by CD21 and CD27 for activated memory (D), resting memory (E), naive/CD27lo memory (F), and atypical (G) B cells or (H) CD11c B cells. Primary infected individuals (blue circles, n = 16) were compared with previously exposed (red boxes, n = 32) and noninfected healthy controls (white circles, n = 14). Data are shown as geometric mean ± 95% CI. Dotted lines correspond to the healthy control geometric mean from a single time point. (I) Mature CD11c+ B cells were correlated with CD21lo B cells (n = 175), corresponding to activated memory and atypical B cells, using linear regression with calculation of Pearson r2. (J) Ki67+ and Ki67− mature B cells were compared for frequency of CD11c+ B cells (n = 26; Wilcoxon matched pairs test).

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