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 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.

• Authors: Daria Donati, Bobo Mok, Arnaud Chêne, Hong Xu, Mathula Thangarajh, Rickard Glas, Qijun Chen, Mats Wahlgren, Maria Teresa Bejarano
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 177 Issue 5 Pg. 3035-44 (Sep 01 2006) ISSN: 0022-1767 [Print] United States
• PMID: 16920940 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Proto-Oncogene Proteins c-bcl-2
• Protozoan Proteins
• erythrocyte membrane protein 1, Plasmodium falciparum

Topics

• Animals
• Antibodies (immunology)
• B-Lymphocytes (cytology, immunology, metabolism)
• Cell Survival
• Cells, Cultured
• Gene Expression Profiling
• Gene Expression Regulation
• Humans
• Immunologic Memory (immunology)
• Lymphocyte Activation (immunology)
• Malaria (immunology)
• Phenotype
• Plasmodium falciparum (immunology)
• Protein Binding
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Protozoan Proteins (genetics, immunology)