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

Abstract

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.

Proinflammatory Responses and Higher IL-10 Production by T Cells Correlate with Protection against Malaria during Pregnancy and Delivery Outcomes

“…Eotaxin concentrations were decreased in pregnancy (27,30) and correlated very well with Treg frequencies, but the latter did not express the main eotaxin receptor CCR3, which suggests that this chemokine is not involved in the redistribution of Tregs during pregnancy. We were surprised to find a relatively strong negative correlation between IL-12 concentration and T H 1 cell frequency and between TGF-b concentration and Treg frequency, because these cytokines are known to trigger differentiation of those cellular subsets.…”

“…5A), and a negative correlation with TGF-b (q = 0.009). Eotaxin levels are decreased during pregnancy and in individuals exposed to malaria (27,30). We have previously demonstrated that memory B cells express eotaxin receptor CCR3 (27) and activated murine Tregs express also this receptor (31).…”

“…Eotaxin levels are decreased during pregnancy and in individuals exposed to malaria (27,30). We have previously demonstrated that memory B cells express eotaxin receptor CCR3 (27) and activated murine Tregs express also this receptor (31). Thus, although eotaxin is not a classical T cell chemokine, we decided to investigate whether human Tregs express CCR3 and might respond to eotaxin.…”

T follicular helper cells regulate the activation of B lymphocytes and antibody production during Plasmodium vivax infection

“…Previous study showed that higher proportions of IgD - atypical memory B cells are observed in P . vivax exposed pregnant and non-pregnant women compared to non-exposed individuals [57]. An controlled P .…”

The immunological balance between host and parasite in malaria

“…Furthermore, whether atypical MBCs differentiate from classical MBCs or whether they originate from different precursors is still controversial (Muellenbeck et al 2013;Portugal et al 2015). An expanded atypical MBC pool is found in people who are chronically exposed to or infected with malaria, and a higher frequency of atypical MBCs is found in patients who reported at least one previous malaria episode compared to no previous exposure (Weiss et al 2009(Weiss et al , 2011Illingworth et al 2013;Ampomah et al 2014;Requena et al 2014). These atypical MBCs upregulate inhibitory receptors such as Fc receptor ligand 3 (FcRL3) and FcRL5, and show diminished BCR signaling, proliferation, and cytokine production (Portugal et al 2015;Sullivan et al 2015).…”