Increased B cell survival and preferential activation of the memory compartment by a malaria polyclonal B cell activator.
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 1alpha (CIDR1alpha) 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 CIDR1alpha to human IgM and IgG is relatively low, B cell activation still proceeds. CIDR1alpha 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 CIDR1alpha preferentially activates memory B lymphocytes. Analysis of the gene expression profiles induced by CIDR1alpha 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 CIDR1alpha 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 CIDR1alpha is of relevance for understanding the mechanisms behind the increased risk of Burkitt's lymphoma in malaria endemic areas.
Donati
Daria
D
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. daria.donati@ki.se
Mok
Bobo
B
Chêne
Arnaud
A
Xu
Hong
H
Thangarajh
Mathula
M
Glas
Rickard
R
Chen
Qijun
Q
Wahlgren
Mats
M
Bejarano
Maria Teresa
MT
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008288:Malaria / Q000276:immunology*; D010641:Phenotype; D010963:Plasmodium falciparum / Q000276:immunology*; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology
D000906:Antibodies; D019253:Proto-Oncogene Proteins c-bcl-2; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum