Atypical and classical memory B cells produce <i>Plasmodium falciparum</i> neutralizing antibodies

Muellenbeck, Matthias F; Ueberheide, Beatrix; Amulic, Borko; Epp, Alexandra; Fenyö, David; Busse, Christian E.; Esen, Meral; Theisen, Michael; Mordmüller, Benjamin; Wardemann, Hedda

doi:10.1084/jem.20121970

Cited by 190 publications

(265 citation statements)

References 48 publications

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“…We also found no associations between atypical MBC and poor pregnancy outcomes. This is in agreement with the finding that atypical MBC can produce regular amounts of functional IgG (25,26). However, the increased levels of atypical MBC after malaria exposure might have an impact on other diseases beyond malaria due to a potential role in innate immunity.…”

Section: Discussionsupporting

confidence: 91%

“…A potential role of active atypical MBC as a special class of short-lived plasma cells has also been proposed (25,26). Consistent with this lineage, in which surface Ig expression is downregulated in favor of transition to secretory Ig (53), we did observe a lower amount of surface IgG (MFI levels) in active atypical MBC compared with the mean IgG levels in B cells in the NP, ENP, and EP groups.…”

Section: Discussionsupporting

confidence: 83%

“…The profiles of cytokines/chemokines that correlated with active and resting classical MBC were similar, whereas inverse profiles correlated with naive B cells. The profile of cytokines/chemokines associated with MZ-like MBC and atypical MBC did not cluster with that of naive or classical MBC, suggesting a different developmental origin (26). MZ-like MBC had a borderline significant positive correlation with RANTES (adjusted p = 0.054).…”

Section: Correlation Between B Cells and Plasma Cytokine And Chemokinmentioning

confidence: 89%

“…However, the increased levels of atypical MBC after malaria exposure might have an impact on other diseases beyond malaria due to a potential role in innate immunity. Malaria exposure induces atypical MBC to express the inhibitory receptor Fc receptor-like protein (FcRL) 4 (21,26). FcRL4 dampens BCR activation, but enhances TLR9 signaling, favoring a switch from adaptive to innate B cell signaling (51).…”

Section: Discussionmentioning

confidence: 99%

“…Two different studies have established that, unlike HIV, the malaria-driven expanded atypical MBC population produces regular amounts of functional Abs (25,26). Moreover, it seems that Ab and especially MBC responses to malaria Ags can be stably maintained over time in the absence of reinfection (27,28).…”

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confidence: 99%

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Pregnancy and Malaria Exposure Are Associated with Changes in the B Cell Pool and in Plasma Eotaxin Levels

Requena

Campo

Umbers

et al. 2014

The Journal of Immunology

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Pregnancy triggers immunological changes aimed to tolerate the fetus, but its impact on B lymphocytes is poorly understood. In addition, exposure to the Plasmodium parasite is associated with altered distribution of peripheral memory B cell (MBC) subsets. To study the combined impact of high malaria exposure and pregnancy in B cell subpopulations, we analyzed PBMCs from pregnant and nonpregnant individuals from a malaria-nonendemic country (Spain) and from a high malaria-endemic country (Papua New Guinea). In the malaria-naive cohorts, pregnancy was associated with a significant expansion of all switched (IgD−) MBC and a decrease of naive B cells. Malaria-exposed women had more atypical MBC and fewer marginal zone–like MBC, and their levels correlated with both Plasmodium vivax– and Plasmodium falciparum–specific plasma IgG levels. Classical but not atypical MBC were increased in P. falciparum infections. Moreover, active atypical MBC positively correlated with proinflammatory cytokine plasma concentrations and had lower surface IgG levels than the average. Decreased plasma eotaxin (CCL11) levels were associated with pregnancy and malaria exposure and also correlated with B cell subset frequencies. Additionally, active atypical and active classical MBC expressed higher levels of eotaxin receptor CCR3 than the other B cell subsets, suggesting a chemotactic effect of eotaxin on these B cell subsets. These findings are important to understand immunity to infections like malaria that result in negative outcomes for both the mother and the newborn and may have important implications on vaccine development.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 83%

Section: Correlation Between B Cells and Plasma Cytokine And Chemokinmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Pregnancy and Malaria Exposure Are Associated with Changes in the B Cell Pool and in Plasma Eotaxin Levels

Requena

Campo

Umbers

et al. 2014

The Journal of Immunology

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The immune response in mild and severe malaria

Waisberg

Crompton

Miller

2016

Advances in Malaria Research

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Long‐lived Plasmodium falciparum specific memory B cells in naturally exposed Swedish travelers

et al. 2013

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Antibodies (Abs) are critical for immunity to malaria. However, Plasmodium falciparum specific Abs decline rapidly in absence of reinfection, suggesting impaired immunological memory. This study determines whether residents of Sweden that were treated for malaria following international travel maintained long‐lasting malaria‐specific Abs and memory B cells (MBCs). We compared levels of malaria‐specific Abs and MBCs between 47 travelers who had been admitted with malaria at the Karolinska University Hospital between 1 and 16 years previously, eight malaria‐naïve adult Swedes without histories of travel, and 14 malaria‐immune adult Kenyans. Plasmodium falciparum‐lysate‐specific Ab levels were above naïve control levels in 30% of the travelers, whereas AMA‐1, merozoite surface protein‐142, and merozoite surface protein‐3‐specific Ab levels were similar. In contrast, 78% of travelers had IgG‐MBCs specific for at least one malaria antigen (59, 45, and 28% for apical merozoite antigen‐1, merozoite surface protein‐1, and merozoite surface protein‐3, respectively) suggesting that malaria‐specific MBCs are maintained for longer than the cognate serum Abs in the absence of re‐exposure to parasites. Five travelers maintained malaria antigen‐specific MBC responses for up to 16 years since the diagnosis of the index episode (and had not traveled to malaria‐endemic regions in the intervening time). Thus P. falciparum can induce long‐lasting MBCs, maintained for up to 16 years without reexposure.

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Atypical and classical memory B cells produce Plasmodium falciparum neutralizing antibodies

Abstract: Plasmodium falciparum infection leads to the development of protective classical and atypical memory B cell antibody responses.

Cited by 190 publications

References 48 publications

Pregnancy and Malaria Exposure Are Associated with Changes in the B Cell Pool and in Plasma Eotaxin Levels

Pregnancy and Malaria Exposure Are Associated with Changes in the B Cell Pool and in Plasma Eotaxin Levels

The immune response in mild and severe malaria

Long‐lived Plasmodium falciparum specific memory B cells in naturally exposed Swedish travelers

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