Discordant memory B cell and circulating anti-Env antibody responses in HIV-1 infection

Long-lived memory B cells (B(Mem)) provide an archive of historic Ab responses. By contrast, circulating Abs typically decline once the immunogen is cleared. Consequently, circulating Abs can underestimate the nature of cognate humoral immunity. On the other hand, the B(Mem) pool should provide a comprehensive picture of Ab specificities that arise over the entire course of infection. To test this hypothesis, we compared circulating Ab and B(Mem) from natural virus suppressors who control HIV-1 without therapy and maintain a relatively intact immune system. We found high frequencies of B(Mem) specific for the conserved neutralizing CD4 induced or CD4 binding site epitopes of gp120, whereas low Ab titers to these determinants were detected in contemporaneous plasma. These data suggest that plasma Ab repertoires can underestimate the breadth of humoral immunity, and analyses of B(Mem) should be included in studies correlating Ab specificity with protective immunity to HIV-1.