221 Humoral Immunity against Conserved Epitopes of HIV-1 Envelope Protein Archived in Memory B cells in Natural Viral Suppressors: Discordance with Plasma Antibodies:

Long-lived memory B cells (BMem) are an archive of past antibody (Ab) responses that persists for much of the host lifespan. By contrast, circulating antibodies typically decline to low or undetectable levels once the immunogen is cleared. This raises the possibility that the BMem pool might provide a more accurate picture of discrete antibody specificities that arise and decline during the course of an antibody response. This could be especially important for correlating antibody specificity with protective immunity in infectious diseases such as AIDS. By studying Ab and BMem of HIV-1 infected individuals who naturally suppress HIV-1 without therapy (NVS), we found high frequencies of BMem specific for CD4 induced (CD4i) or CD4 binding site (CD4bs) epitopes of gp120 that were discordant with contemporaneous plasma antibody responses to these epitopes. These data suggest that plasma Ab responses can underestimate the breadth of humoral immunity and that analyses of BMem should be included in studies correlating antibody specificity with protective immunity to HIV-1. In addition, a novel strategy to rapid selectively clone human monoclonal antibody (mAb) from BMem was developed and 25 novel mAbs of CD4i or CD4bs were obtained.