The V gene repertoires of classical and atypical memory B cells in malaria-susceptible West African children

Immunity to Plasmodium falciparum malaria is naturally acquired in individuals living in malaria-endemic areas of Africa. Abs play a key role in mediating this immunity; however, the acquisition of the components of Ab immunity, long-lived plasma cells and memory B cells (MBCs), is remarkably inefficient, requiring years of malaria exposure. Although long-lived classical MBCs (CD19+/CD20+/CD21+/CD27+/CD10-) are gradually acquired in response to natural infection, exposure to P. falciparum also results in a large expansion of what we have termed atypical MBCs (CD19+/CD20+/CD21-/CD27-/CD10-). At present, the function of atypical MBCs in malaria is not known, nor are the factors that drive their differentiation. To gain insight into the relationship between classical and atypical IgG+ MBCs, we compared the Ab H and L chain V gene repertoires of children living in a malaria-endemic region in Mali. We found that these repertoires were remarkably similar by a variety of criteria, including V gene usage, rate of somatic hypermutation, and CDR-H3 length and composition. The similarity in these repertoires suggests that classical MBCs and atypical MBCs differentiate in response to similar Ag-dependent selective pressures in malaria-exposed children and that atypical MBCs do not express a unique V gene repertoire.