Increased B Cell Survival and Preferential Activation of the Memory Compartment by a Malaria Polyclonal B Cell Activator

Abstract

Chronic malaria infection is characterized by polyclonal B cell activation, hyperglobulinemia, and elevated titers of autoantibodies. We have recently identified the cysteine-rich interdomain region 1α (CIDR1α) of the Plasmodium falciparum erythrocyte membrane protein 1 as a T cell-independent polyclonal B cell activator and Ig binding protein. Here, we show that, although the binding affinity of CIDR1α to human IgM and IgG is relatively low, B cell activation still proceeds. CIDR1α rescues tonsillar B cells from apoptosis, and increases the proportion of cycling cells. Comparison of the impact on naive and memory B cell compartment indicated that CIDR1α preferentially activates memory B lymphocytes. Analysis of the gene expression profiles induced by CIDR1α and anti-Ig activation using a cDNA microarray demonstrated a low degree of homology in the signatures imposed by both stimuli. The microarray data correlate with the functional analysis demonstrating that CIDR1α activates various immunological pathways and protects B cells from apoptosis. Together, the results provide evidence for a role of malaria in preferentially activating the memory B cell compartment. The polyclonal B cell activation and augmented survival induced by CIDR1α is of relevance for understanding the mechanisms behind the increased risk of Burkitt’s lymphoma in malaria endemic areas.

The role of platelet and plasma markers of antioxidant status and oxidative stress in thrombocytopenia among patients with vivax malaria

“…In the present study, the auto-antibodies reactive to LDL -, expressed as the ratio between antibodies anti-LDL -and anti-native LDL, were lower in TCP than in NTCP. However, the amount of anti-native LDL was 2.5 times higher in TCP, which is probably due to the polyclonal B cell activation observed in chronic malaria infection (Donati et al 2006).…”

Q Fever in Young Children, Ghana

“…However, because consumption of raw milk in the Ashanti region is regarded as being uncommon by local health authorities, we consider dairy products an unlikely source of the disease. Although participants were intensively exposed to P. falciparum, which causes polyclonal Bcell stimulation, malaria episodes and parasitemia with and without symptoms at time of the serosurvey did not infl uence testing (10). This fi nding is important because commercially available test kits have only been evaluated in Europeans not exposed to parasites.…”

Epstein‐Barr virus and the pathogenesis of Burkitt's lymphoma: More questions than answers

“…HIV gp120 has been reported to act as a superantigen stimulating VH3 expressing B cells in vitro and in vivo, followed by an exhaustion of VH3 expressing B cells during progression of the disease. [57][58][59] In malaria, the cysteine-rich interdomain region 1alpha (CIDR1alpha) of P. falciparum erythrocyte membrane protein 1 (PfEMP1) expressed in red blood cells was shown to act not only as a polyclonal B cell activator 60,61 but also as an inducer of EBVs lytic cycle. 62 Taking together, the important risk factor imposed by malaria and HIV is the potent polyclonal B cell activation 63,64 that may be additionally associated with higher virus titers and an increase in the number of EBV-infected memory B cells in vivo.…”