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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 7

Dynamic expression of FcRL5 and CXCR3 among CD11c+ B cell subsets.

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Dynamic expression of FcRL5 and CXCR3 among CD11c+ B cell subsets.
(A) R...
(A) Representative graph showing gating of CD11c+ and CD11c– mature B cells (CD19+CD20+CD10−) from 1 previously exposed donor at 10 days after acute infection (left). Representative expression levels of CD20, CD19, CD21, CD85j, CXCR3, and FcRL5 between CD11c− (filled histograms) and CD11c+ (open histograms) populations from the same donor. (B) MFI ratio between CD11c+ and CD11c– mature B cells for CD21 (circles), CD85j (boxes), CD20 (diamonds), CXCR3 (triangles), and FcRL5 (crosses) at each sample time point. Data represent both primary infected and previously exposed individuals (n = 49). (C) Frequency of FcRL5+ cells among total CD11c+ mature B cells or (D) further separated based on expression of CD21 and CD27. (E) Frequency of CXCR3+ cells among total CD11c+ mature B cells or (F) further separated based on expression of CD21 and CD27. (C–F) Data show geometric mean with error bars indicating ± 95% CI. Primary infected individuals are indicated by blue circles (n = 16), previously exposed individuals by red boxes (n = 33), and healthy controls by white circles (n = 14). The dotted line indicates the geometric mean of the healthy controls.

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