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A positive correlation between atypical memory B cells and Plasmodium falciparum transmission intensity in cross-sectional studies in Peru and Mali.

Weiss GE, Clark EH, Li S, Traore B, Kayentao K, Ongoiba A, Hernandez JN, Doumbo OK, Pierce SK, Branch OH, Crompton PD - PLoS ONE (2011)

Bottom Line: In Peru, the mean level of atypical memory B cells, as a percent of total B cells, was higher than U.S. adults (Peru mean: 5.4% [95% CI: 3.61-7.28]; U.S. mean: 1.4% [95% CI: 0.92-1.81]; p<0.0001) but lower than Malian adults (Mali mean 13.1% [95% CI: 10.68-15.57]; p = 0.0001).In Peru, individuals self-reporting ≥1 prior malaria episodes had a higher percentage of atypical memory B cells compared to those reporting no prior episodes (≥1 prior episodes mean: 6.6% [95% CI: 4.09-9.11]; no prior episodes mean: 3.1% [95% CI: 1.52-4.73]; p = 0.028).Understanding the origin, function and antigen specificity of atypical memory B cells in the context of Pf infection could contribute to our understanding of naturally-acquired malaria immunity.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.

ABSTRACT

Background: Antibodies that protect against Plasmodium falciparum (Pf) malaria are only acquired after years of repeated infections. The B cell biology that underlies this observation is poorly understood. We previously reported that "atypical" memory B cells are increased in children and adults exposed to intense Pf transmission in Mali, similar to what has been observed in individuals infected with HIV. In this study we examined B cell subsets of Pf -infected adults in Peru and Mali to determine if Pf transmission intensity correlates with atypical memory B cell expansion.

Methodology/principal findings: In this cross-sectional study venous blood was collected from adults in areas of zero (U.S., n = 10), low (Peru, n = 18) and high (Mali, n = 12) Pf transmission. Adults in Peru and Mali were infected with Pf at the time of blood collection. Thawed lymphocytes were analyzed by flow cytometry to quantify B cell subsets, including atypical memory B cells, defined by the cell surface markers CD19(+) CD20(+) CD21(-) CD27(-) CD10(-). In Peru, the mean level of atypical memory B cells, as a percent of total B cells, was higher than U.S. adults (Peru mean: 5.4% [95% CI: 3.61-7.28]; U.S. mean: 1.4% [95% CI: 0.92-1.81]; p<0.0001) but lower than Malian adults (Mali mean 13.1% [95% CI: 10.68-15.57]; p = 0.0001). In Peru, individuals self-reporting ≥1 prior malaria episodes had a higher percentage of atypical memory B cells compared to those reporting no prior episodes (≥1 prior episodes mean: 6.6% [95% CI: 4.09-9.11]; no prior episodes mean: 3.1% [95% CI: 1.52-4.73]; p = 0.028).

Conclusions/significance: Compared to Pf-naive controls, atypical memory B cells were increased in Peruvian adults exposed to low Pf transmission, and further increased in Malian adults exposed to intense Pf transmission. Understanding the origin, function and antigen specificity of atypical memory B cells in the context of Pf infection could contribute to our understanding of naturally-acquired malaria immunity.

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Atypical MBCs in individuals from the U.S., Peru and Mali.Atypical MBCs were detected by flow cytometry and expressed as a percentage of total B cells in the peripheral blood of Pf-naive U.S. adults (n = 10), Pf-infected Peruvian adults (n = 18) and Pf-infected Malian adults (n = 12). Box-and-whisker plots represent the smallest and largest values (whiskers), the lower and upper quartiles (top and bottom of box), and the median (horizontal line across box). The Mann-Whitney test was used to compare continuous variables between groups.
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pone-0015983-g001: Atypical MBCs in individuals from the U.S., Peru and Mali.Atypical MBCs were detected by flow cytometry and expressed as a percentage of total B cells in the peripheral blood of Pf-naive U.S. adults (n = 10), Pf-infected Peruvian adults (n = 18) and Pf-infected Malian adults (n = 12). Box-and-whisker plots represent the smallest and largest values (whiskers), the lower and upper quartiles (top and bottom of box), and the median (horizontal line across box). The Mann-Whitney test was used to compare continuous variables between groups.

Mentions: We determined if atypical MBCs were detectable in the peripheral blood of Peruvian adults (n = 18) living in an area of low level Pf transmission by performing FACS analysis on thawed PBMCs which had been collected during symptomatic Pf infection. These data were compared to B cell profiles of Pf-naive U.S. adults (n = 10) and Pf-infected asymptomatic Malian adults (n = 12). As a percentage of total B cells, the mean percentage of atypical MBCs in Peruvian adults was higher than the mean percentage in U.S. adults (Fig. 1; Peru: 5.4% [95% CI: 3.6–7.3]; U.S.: 1.4% [95% CI: 0.9–1.8; P<0.0001], but lower than the percentage in Malian adults (Fig. 1; Mali: 13.1% [95% CI: 10.7–15.6]; P = 0.0001 versus Peru]. The low percentage of atypical MBCs in the peripheral blood of healthy U.S. adults is consistent with other reports [17]. Stratifying Peruvian adults by a self-reported history of prior malaria episodes revealed that the mean percentage of atypical MBCs was higher in those reporting at least one prior malaria episode (n = 12), versus those who reported no prior malaria episodes (n = 6) (Fig. 2; no prior malaria reported: 3.1% [95% CI: 1.5–4.7]; prior malaria reported: 6.6% [95% CI: 4.1–9.1; P = 0.028]. Together these data suggest that atypical MBCs increase as a percentage of total B cells with increasing Pf exposure.


A positive correlation between atypical memory B cells and Plasmodium falciparum transmission intensity in cross-sectional studies in Peru and Mali.

Weiss GE, Clark EH, Li S, Traore B, Kayentao K, Ongoiba A, Hernandez JN, Doumbo OK, Pierce SK, Branch OH, Crompton PD - PLoS ONE (2011)

Atypical MBCs in individuals from the U.S., Peru and Mali.Atypical MBCs were detected by flow cytometry and expressed as a percentage of total B cells in the peripheral blood of Pf-naive U.S. adults (n = 10), Pf-infected Peruvian adults (n = 18) and Pf-infected Malian adults (n = 12). Box-and-whisker plots represent the smallest and largest values (whiskers), the lower and upper quartiles (top and bottom of box), and the median (horizontal line across box). The Mann-Whitney test was used to compare continuous variables between groups.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3021525&req=5

pone-0015983-g001: Atypical MBCs in individuals from the U.S., Peru and Mali.Atypical MBCs were detected by flow cytometry and expressed as a percentage of total B cells in the peripheral blood of Pf-naive U.S. adults (n = 10), Pf-infected Peruvian adults (n = 18) and Pf-infected Malian adults (n = 12). Box-and-whisker plots represent the smallest and largest values (whiskers), the lower and upper quartiles (top and bottom of box), and the median (horizontal line across box). The Mann-Whitney test was used to compare continuous variables between groups.
Mentions: We determined if atypical MBCs were detectable in the peripheral blood of Peruvian adults (n = 18) living in an area of low level Pf transmission by performing FACS analysis on thawed PBMCs which had been collected during symptomatic Pf infection. These data were compared to B cell profiles of Pf-naive U.S. adults (n = 10) and Pf-infected asymptomatic Malian adults (n = 12). As a percentage of total B cells, the mean percentage of atypical MBCs in Peruvian adults was higher than the mean percentage in U.S. adults (Fig. 1; Peru: 5.4% [95% CI: 3.6–7.3]; U.S.: 1.4% [95% CI: 0.9–1.8; P<0.0001], but lower than the percentage in Malian adults (Fig. 1; Mali: 13.1% [95% CI: 10.7–15.6]; P = 0.0001 versus Peru]. The low percentage of atypical MBCs in the peripheral blood of healthy U.S. adults is consistent with other reports [17]. Stratifying Peruvian adults by a self-reported history of prior malaria episodes revealed that the mean percentage of atypical MBCs was higher in those reporting at least one prior malaria episode (n = 12), versus those who reported no prior malaria episodes (n = 6) (Fig. 2; no prior malaria reported: 3.1% [95% CI: 1.5–4.7]; prior malaria reported: 6.6% [95% CI: 4.1–9.1; P = 0.028]. Together these data suggest that atypical MBCs increase as a percentage of total B cells with increasing Pf exposure.

Bottom Line: In Peru, the mean level of atypical memory B cells, as a percent of total B cells, was higher than U.S. adults (Peru mean: 5.4% [95% CI: 3.61-7.28]; U.S. mean: 1.4% [95% CI: 0.92-1.81]; p<0.0001) but lower than Malian adults (Mali mean 13.1% [95% CI: 10.68-15.57]; p = 0.0001).In Peru, individuals self-reporting ≥1 prior malaria episodes had a higher percentage of atypical memory B cells compared to those reporting no prior episodes (≥1 prior episodes mean: 6.6% [95% CI: 4.09-9.11]; no prior episodes mean: 3.1% [95% CI: 1.52-4.73]; p = 0.028).Understanding the origin, function and antigen specificity of atypical memory B cells in the context of Pf infection could contribute to our understanding of naturally-acquired malaria immunity.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.

ABSTRACT

Background: Antibodies that protect against Plasmodium falciparum (Pf) malaria are only acquired after years of repeated infections. The B cell biology that underlies this observation is poorly understood. We previously reported that "atypical" memory B cells are increased in children and adults exposed to intense Pf transmission in Mali, similar to what has been observed in individuals infected with HIV. In this study we examined B cell subsets of Pf -infected adults in Peru and Mali to determine if Pf transmission intensity correlates with atypical memory B cell expansion.

Methodology/principal findings: In this cross-sectional study venous blood was collected from adults in areas of zero (U.S., n = 10), low (Peru, n = 18) and high (Mali, n = 12) Pf transmission. Adults in Peru and Mali were infected with Pf at the time of blood collection. Thawed lymphocytes were analyzed by flow cytometry to quantify B cell subsets, including atypical memory B cells, defined by the cell surface markers CD19(+) CD20(+) CD21(-) CD27(-) CD10(-). In Peru, the mean level of atypical memory B cells, as a percent of total B cells, was higher than U.S. adults (Peru mean: 5.4% [95% CI: 3.61-7.28]; U.S. mean: 1.4% [95% CI: 0.92-1.81]; p<0.0001) but lower than Malian adults (Mali mean 13.1% [95% CI: 10.68-15.57]; p = 0.0001). In Peru, individuals self-reporting ≥1 prior malaria episodes had a higher percentage of atypical memory B cells compared to those reporting no prior episodes (≥1 prior episodes mean: 6.6% [95% CI: 4.09-9.11]; no prior episodes mean: 3.1% [95% CI: 1.52-4.73]; p = 0.028).

Conclusions/significance: Compared to Pf-naive controls, atypical memory B cells were increased in Peruvian adults exposed to low Pf transmission, and further increased in Malian adults exposed to intense Pf transmission. Understanding the origin, function and antigen specificity of atypical memory B cells in the context of Pf infection could contribute to our understanding of naturally-acquired malaria immunity.

Show MeSH
Related in: MedlinePlus