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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 5

CD11c B cell subset kinetics in primary infected and previously exposed individuals.

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CD11c B cell subset kinetics in primary infected and previously exposed ...
(A) Schematic gating strategy for CD11c+ B cells followed by CD21 versus CD27 in one previously exposed donor at the acute, 10-day and 1-, 3-, 6-, and 12-month time points. (B) Frequency of CD11c+ B cells further separated based on expression of CD21 and CD27. (C) Cell numbers per thousand live lymphocyte singlets for CD11c+ B cells indicated in A. Statistical differences between groups were assessed using a linear mixed-effects model, with the P value indicated in the graphs. Primary infected individuals are indicated by blue circles (n = 16), and previously exposed individuals by red boxes (n = 33). Symbols indicate geometric mean with error bars showing ± 95% CI.

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