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* Microbiology and Tumorbiology Center, Karolinska Institutet,
Center for Infectious Medicine, Department of Medicine,
Division of Neurology R54, Karolinska Institutet, Karolinska University Hospital Huddinge, and
Swedish Institute for Infection Disease Control, Stockholm, Sweden
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 1
(CIDR1) 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 CIDR1 to human IgM and IgG is relatively low, B cell activation still proceeds. CIDR1 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 CIDR1 preferentially activates memory B lymphocytes. Analysis of the gene expression profiles induced by CIDR1 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 CIDR1 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 CIDR1 is of relevance for understanding the mechanisms behind the increased risk of Burkitt’s lymphoma in malaria endemic areas.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Swedish International Development Cooperation Agency, Barncancerfonden, the Swedish Research Council, the Swedish Foundation for Strategic Research, and the Karolinska Institutet.
2 Address correspondence and reprint requests to Dr. Daria Donati, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, F59, SE-141 86 Stockholm, Sweden. E-mail address: daria.donati{at}ki.se
3 Abbreviations used in this paper: IE, infected erythrocyte; PfEMP1, Plasmodium falciparum erythrocyte membrane protein 1; IBP, Ig binding protein; CIDR1, cysteine-rich interdomain region 1; PI, propidium iodide; XIAP, X-linked inhibitor of apoptosis; APRIL, a proliferation-inducing ligand; GC, germinal center; CT, cycle threshold.
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