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 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.