The molecular identity of VSAPAM remains controversial, although current evidence points to VAR2CSA, an interclonally conserved member of the PfEMP1 molecules encoded by the multigene var family. Thus, transcription of the gene encoding VAR2CSA is increased among CSAadhering and placental isolates, VAR2CSA is exposed on the surface of CSA-adhering IEs (Salanti et al., 2003; 2004; Tuikue Ndam et al., 2005) , and plasma levels of VAR2CSA-specific IgG increase with increasing parity and correlate with protective immunity to PAM (Salanti et al., 2004) . However, the importance of VAR2CSAspecific antibodies relative to antibodies specific for other putative VSA PAM in acquired protective immunity to PAM remains to be established. The clonal analysis of memory B cells represents a powerful tool to dissect the immune response to complex pathogens such as P. falciparum (Lanzavecchia et al., 2006) . In this study, we used an improved Epstein-Barr virus (EBV) immortalization method (Traggiai et al., 2004) to analyse memory B cells from multiparous PAM-exposed women. Frequency analysis and isolation of specific monoclonal antibodies identified polymorphic, linear and conformationdependent epitopes in VAR2CSA as dominant targets of the human memory B-cell response to PAM.