Obeng-Adjei et al. found that the inefficient acquisition of humoral responses to malaria in children is neither due to a deficiency in the generation and maintenance of memory Tfh cells nor to an altered distribution of Tfh cell subsets, but to the preferential activation of a Th1 polarized CD4+PD1+CXCR3+CXCR5+ subpopulation during acute malaria infection. The gene discussed is CXCR5; the disease is malaria.