Chronic Exposure to Malaria Is Associated with Inhibitory and Activation Markers on Atypical Memory B Cells and Marginal Zone-Like B Cells

Abstract

In persistent infections that are accompanied by chronic immune activation, such as human immunodeficiency virus, hepatitis C virus, and malaria, there is an increased frequency of a phenotypically distinct subset of memory B cells lacking the classic memory marker CD27 and showing a reduced capacity to produce antibodies. However, critical knowledge gaps remain on specific B cell changes and immune adaptation in chronic infections. We hypothesized that expansion of atypical memory B cells (aMBCs) and reduction of activated peripheral marginal zone (MZ)-like B cells in constantly exposed individuals might be accompanied by phenotypic changes that would confer a tolerogenic profile, helping to establish tolerance to infections. To better understand malaria-associated phenotypic abnormalities on B cells, we analyzed peripheral blood mononuclear cells from 55 pregnant women living in a malaria-endemic area of Papua Nueva Guinea and 9 Spanish malaria-naïve individuals using four 11-color flow cytometry panels. We assessed the expression of markers of B cell specificity (IgG and IgM), activation (CD40, CD80, CD86, b220, TACI, and CD150), inhibition (PD1, CD95, and CD71), and migration (CCR3, CXCR3, and CD62l). We found higher frequencies of active and resting aMBC and marked reduction of MZ-like B cells, although changes in absolute cell counts could not be assessed. Highly exposed women had higher PD1+-, CD95+-, CD40+-, CD71+-, and CD80+-activated aMBC frequencies than non-exposed subjects. Malaria exposure increased frequencies of b220 and proapoptotic markers PD1 and CD95, and decreased expression of the activation marker TACI on MZ-like B cells. The increased frequencies of inhibitory and apoptotic markers on activated aMBCs and MZ-like B cells in malaria-exposed adults suggest an immune-homeostatic mechanism for maintaining B cell development and function while simultaneously downregulating hyperreactive B cells. This mechanism would keep the B cell activation threshold high enough to control infection but impaired enough to tolerate it, preventing systemic inflammation.

IL-10–producing B cells are enriched in murine pericardial adipose tissues and ameliorate the outcome of acute myocardial infarction

“…S1B). While the mechanism remains unclear, possibly due to the response by B cells to inflammation (49), it limited us in identifying B-1 cells and their subsets during acute MI utilizing the feature of the low to intermediate level of B220 expression on these cells (50). Because CD5 predominantly marks B-1a cells in the B cell compartment (50), we sought to examine CD5 + B cells as a surrogate for B-1a cells (Fig.…”

Baseline exposure, antibody subclass, and hepatitis B response differentially affect malaria protective immunity following RTS,S/AS01E vaccination in African children

“…We and others have shown that malaria exposure alters the phenotype and functional characteristics of memory B lymphocytes [ 46 , 47 ] and other cells, e.g., T helper [ 48 ], that are responsible for antibody production. Individuals under higher MTI may have an immune system that is suppressed, de-regulated, or primed by natural exposure to produce a different immune response that upon RTS,S vaccination could deviate CSP response to predominantly non-cytophilic antibodies and/or overall lower IgG levels.…”

Targeting B Cells and Plasma Cells in Autoimmune Diseases

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